23, 2013 Lyon, France Annual Congress of the European Association ...

EANM´13

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A s s o ci atio n o f N u cl e a r M e d i

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Continuing Medical Education Extended Abstracts

Annual Congress of the European Association of Nuclear Medicine October 19 –23, 2013 Lyon, France www.eanm.org

Annual Congress of the European Association of Nuclear Medicine

Union Européenne des médicins specialists European union of medical specialists

European School of Nuclear Medicine Continuing Medical Education at the Annual Congress of the European Association of Nuclear Medicine, Lyon October 19 – October 23, 2013 The European School of Nuclear Medicine is accredited by the European Accreditation Council for Continuing Medical Education (EACCME) to provide the following CME activity for medical specialists. The EACCME is an institution of the European Union of Medical Specialists (UEMS), www.uems.net. The Continuing Medical Education at the Annual Congress of the European Association of Nuclear Medicine (EANM’13 Lyon, October 19 – 23, 2013) is designated for a maximum of 19,5 hours of European external CME credits (ECMECs). Each medical specialist should claim only those hours of credit that he/she actually spent in the Educational Facility. ECMECs are recognized by the American Medical Association towards the Physician’s Recognition Award (PRA). To convert ECMECs to AMA PRA category 1 credit, contact the AMA.

Annual Congress of the European Association of Nuclear Medicine CCC – Cité Centre de Congrès Lyon, France 19 – 23 October, 2013 Continuing Medical Education Extended Abstracts CME sessions during EANM’13 Lyon are organized by the European School of Nuclear Medicine Dean: C.A. Hoefnagel (Amsterdam) Vice Dean: I. Szilvasi (Budapest) Members: T.V. Bogsrud (Oslo) L. Mansi (Naples) J.N. Talbot (Paris) Education Representatives of the Committees: K. Bacher (Gent) M. Behe (Vlligen) R.D. Bolton (Madrid) M. De Jong (Rotterdam) C. De Labriolle-Vaylet (Paris) C. Hindorf (Lund) O. Israel (Haifa) O. Lindner (Oyenhausen) S. Pappata (Naples) F. Paycha (Paris) C. Pestean (Cluj) N. Ristevska (Skopje) M. Stokkel (Bennebroek) A. Windhorst (Amsterdam)

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October 19 – 23, 2013 · Lyon · France


Table of Contents Introduction by the Dean of the European School of Nuclear Medicine . . . . . . . .

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CME I: Oncology & Drug Development PET and SPECT in Oncology Drug Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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The Basis of Drug Development in Oncology: General Point of View; from Pre-clinical to Clinical Aspects I. Ray-Coquard (Lyon) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Translational PET/SPECT Imaging in Oncology Drug Development: A Pharmaceutical Industry Point of View M. Bergstroem (Basel) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Current Application of PET and SPECT Imaging in Drug Development in Oncology: The Nuclear Physician Point of View W.J.G. Oyen (Nijmegen). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CME II: Radionuclide Therapy & Dosimetry PRRT: New Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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The Genomics of Neuroendocrine Tumors: From Gnosis to Sunesis I. M. Modlin (New Haven) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Dosimetry and Radiobiology for PRRT: Clinically Relevant or is it just a Physicist's Hobby? G. Flux (Sutton Surrey) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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PRRT: from the EANM - IAEA - SNM Guidance Document towards Standardization of Individualized Treatments L. Bodei (Milan) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CME III: Physics Motion Correction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Principles of Motion Correction and Gating K. Thielemans (London). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Clinical Use of Cardiac Gating within PET and SPECT P. Knaapen (Amsterdam). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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4D PET/CT for Radiotherapy Treatment Planning D. Thorwarth (Tuebingen) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CME IV: Radiopharmacy & Drug Development State of the Art of Radiopharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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New SPECT Tracers R. Schibli (Zurich) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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New Radiopharmaceuticals for PET P. H. Elsinga (Groningen) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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New Radiopharmaceuticals for Therapy G.-J. Meyer (Hannover) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Critical Appraisal of Viability Assessment H.J. Verberne (Amsterdam) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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SPECT and PET/CT Assessment C. Übleis (Munich) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Cardiac Magnetic Resonance Assessment M. Lombardi (Pisa) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Multimodality Interpretation and Comparison T. H. Schindler (Baltimore) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CME VI: Bone & Joint The Limping Patient - Multimodality Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Unexplained Hip Pain H. K. Mohan (London) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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SPECT/CT in Knee Joints - What is Left for Nuclear Medicine Tests at the Era of MRI? K. Strobel (Luzern) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Foot Pain Unexplained by X-rays F. Paycha (Paris) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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The Referred Pain - When the Causative Lesion Lies Far from the Aching Joint W. van der Bruggen (Doetinchem) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CME VII: Paediatrics Thyroid Diseases in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Hypothyroidism and Hyperthyroidism in Children: Role of Nuclear Medicine B.O. Helal (Orsay) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Paediatric Thyroid Cancer R. Howman-Giles (Sydney) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Dosimetry and Short/Long-Term Consequences of Radioiodine Treatment in Children and Teenagers F. A. Verburg (Aachen) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CME VIII: Inlammation & Infection The Diabetic Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Nuclear Medicine Procedures and Clinical Indications in Diabetic Patients with Infection (With Special Emphasis on FDG Imaging) O. Israel (Haifa) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Diabetic Nephropathy and Imaging of Kidney Infections and Graft Rejection J. Buscombe (Cambridge) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Imaging Cardiovascular Diseases in Diabetic Patients R. Slart (Groningen) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CME IX: Neuroimaging (Interactive) Brain PET Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Printed in accordance with the Austrian Eco-Label for printed matters.

CME V: Cardiovascular Myocardial Viability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CME X: ESNM Faculty (Interactive) PET/CT in Cancers of Unknown Origin or Paraneoplastic Syndromes. . . . . . . . . . .

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CME XI: ESNM Faculty (Interactive) Pitfalls in Nuclear Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CME XII: Oncology Cross-Sectional Imaging in Nuclear Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CT and MR in Musculoskeletal Pathologies: What the Nuclear Physician Should Know G. Tognini (La Spezia) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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SPECT/CT in Benign Bone Diseases G. Mariani (Pisa) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CT and MRI in Abdominal Cancers: What the Nuclear Physician Should Know P. J. Valette (Lyon) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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PET-CT in Abdominal Cancers C. Tychyj-Pinel (Lyon) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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CME XIII: Translational Molecular Imaging: Joint EANM/ESMI Session Optical and Nuclear Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Nuclear and Fluorescent Tracers for Intraoperative Application R. G. Pleijhuis (Groningen) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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PET and Optical Tomography in Small Animals F. Ducongé (Orsay) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Cerenkov Luminescence Imaging S. Maitrejean (Paris) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Table of Contents

Imprint

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Continuing Medical Education (CME) in Nuclear Medicine at the Annual Congress – Lyon 2013: European School of Nuclear Medicine (ESNM)

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Dear Colleagues, Dear Attendees! It is my great pleasure to welcome you to the EANM’13 Programme of Continuing Medical Education. One year after the EANM celebrated its 25th anniversary in Milan, we convene in the capital of gastronomy and therefore it is only appropriate for the European School of Nuclear Medicine (ESNM) to dish up an attractive 13-course gourmet menu of CME sessions. CME in Lyon For the 13th consecutive time the ESNM once again ofers a balanced mix of carefully chosen state-of-the-art lectures, highly popular interactive sessions and interdisciplinary sessions, made possible by the close cooperation of the EANM Committees. While maintaining the commitment to cover a wide range of nuclear medicine topics for CME, the EANM’13 CME Programme also features a more clinically orientated focus in the CME sessions on Monday, October 21, as well as a day with the favoured interactive sessions on Tuesday, October 22, 2013. In accordance with well-established tradition, the ESNM ofers you this book with Extended Abstracts of the CME lectures and will place all presentations on the EANM website (www.eanm.org, under “Education at the congress”) soon after the congress. Members will be informed when the presentations are online. CME presentations at previous congresses can also be found there.

Apart from the CME Programme during the Annual Congress, a variety of Learning Courses are ofered at the European School of Nuclear Medicine in Vienna. The course material is regularly updated and revised with great commitment and attention to detail and new courses are progressively created. Likewise, the ESNM Central and Eastern European (CEE) Seminars are continuously upgraded, while retaining their well-established and highly appreciated characteristics. By this year, 55 of these Seminars have been held throughout the CEE region. In addition the ESNM has embarked on e-Learning, ofering a series of free Webinars and creating a number of Educational Courses, to be accessed through the EANM website. Evaluation is crucial As maintaining the high standard, which has been established over past years, is the minimum expectation for the upcoming lectures, courses and seminars, feedback from participants is of crucial importance. Therefore, we strongly encourage you to ill out the evaluation form at the end of each CME session you have attended. This will not only serve to guide us in improving the quality of the CME Programme, but also provide you with additional accreditation points for each individual session attended. A total of 19,5 hours of ECMECs may be accumulated, on top of the accreditation points you will receive for participation in the Congress. Last year, during the EANM Congress in Milan, a record number of 2345 accreditation certiicates have been awarded. Finally, I wish to express my gratitude to all ESNM members and CME Session organisers for their eforts and their input to this year’s CME Programme, to the speakers for their commitment to sharing their expertise and to you for your interest in the post-graduate CME sessions. With best regards and, once again, a cordial welcome to EANM’13 Lyon,

Cornelis A. Hoefnagel Dean, European School of Nuclear Medicine

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European School of Nuclear Medicine

ESNM activities The Educational Committee of the ESNM, consisting of a small group of faculty members and the Educational Experts of the EANM Committees, aims to provide post-graduate education of the highest and most up-to-date standard. With great dedication the Committee creates a variety of educational programmes tailored to the needs and interests of the audience, and only speakers with the highest expertise in the respective ields are invited.


CME I: Oncology & Drug Development

Abstracts

PET and SPECT in Oncology Drug Development

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1a

ǚ The Basis of Drug Development in Oncology: General Point of View; from Pre-clinical to Clinical Aspects I. Ray-Coquard (Lyon)

Abstracts

Abstract not available

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1b

ǚ Translational PET/SPECT Imaging in Oncology Drug Development: A Pharmaceutical Industry Point of View M. Bergstroem (Basel) Imaging has always been important for the characterization of treatment response in oncology drug development, using tools like CT, MRI and lately FDG-PET as indicators of the potential of a drug under development to have a clinical beneit. In an efort to be more mechanistic and quantitative in the early phases of drug development, and with the hope of reducing the high attrition rate, a wider approach to imaging is searched for. With this focus, structural imaging is complemented with biodistribution imaging and functional imaging where Molecular Imaging with PET and SPECT is obtaining greater attention. This presentation will illustrate how imaging can support this new drive of being mechanistic and follow a question based drug development where the drug’s access to the target, interaction with the target, cellular consequences and tissue responses are requested to be used together with non-imaging biomarkers for optimization and decisions on termination or continuation. With the great variability and complexity of the biology of cancer and the aims to be precise in drug action, even greater demands are placed on preclinical studies to simulate a clinical trial and to qualify the imaging component in its expected use. This in turn requires much greater attention to the speciic pre-clinical model to be used, the mode of implementation of the imaging component and the use of PK/PD modeling already in the preclinical studies. It also implies that human experimental medicine studies need to be more common as prelude to clinical trials including imaging. References Workman P et al. Minimally Invasive Pharmacokinetic and Pharmacodynamic Technologies in Hypothesis-Testing Clinical Trials of Innovative Therapies. Journal of the National Cancer Institute, 2006, Vol. 98, No. 9, May 3, 580-598

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Workman P. How Much Gets there and What Does it Do?: The Need for Better Pharmacokinetic and Pharmacodynamic Endpoints in Contemporary Drug Discovery and Development. Current Pharmaceutical Design, 2003, 9, 891-902

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Tan DSW et al. Biomarker-Driven Early Clinical Trials in Oncology. A Paradigm Shift in Drug Development. Cancer J 2009;15: 406–420

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Bergstrom M et al. Modelling spheroid growth, PET tracer uptake and treatment efects of the Hsp90 inhibitor NVP-AUY922. J Nucl Med. 2008 Jul;49(7):1204-1210

Abstracts

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ǚ Current Application of PET and SPECT Imaging in Drug Development in Oncology: The Nuclear Physician Point of View W.J.G. Oyen (Nijmegen) The role of molecular imaging with PET and SPECT in drug development has become increasingly important in the past decade. Several diferent roles for molecular imaging can be distinguished.

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1. The radiopharmaceutical is a therapeutic that can be imaged (“theragnostics”). [Kam et al. 2012; Sharkey et al. 2011] The most common theragnostic in nuclear medicine is I-131 for assessment and treatment of thyoid carcinoma. More recently, a variety of radiopharmaceuticals have been introduced in the clinic, such radiolabeled peptides and antibodies for various metastatic cancer types and radiolabeled microspheres for treatment of unresectable liver metastases or hepatocellular carcinoma. These radiopharmaceuticals can be imaged for selection of patients eligible for treatement, dosimetry and (re)staging. 2. A radiopharmaceutical is used to assess the presence of receptors for an unlabeled drug. [Oude Munnik et al. 2009; Desar et al. 2010] With the large scale introduction of targeted therapies in medical oncology, there is an increasing need for assessment of targets on tumor cells by e.g. radiolabeled monoclonal antibodies for SPECT and PET. The images not only relect the presence of a target (as immunohistochemistry does as well), but also allow the assessment of target accessibility in vivo. 3. A radiopharmaceutical is used for (early) prediction of the therapeutic efects of an investigational drug (therapy response monitoring). [Herrmann et al, 2011; Soloviev et al. 2012] There is a wealth of literature available on the use of PET for therapy response monitoring, predominatly using FDG-PET/CT, but also other agents such as FLT-PET/CT. For a wide variety of cancers there is evidence that molecular imaging can predict response earlier than conventional imaging using RECIST. Furthermore, reliable and early prediction of therapy resistance ofers the chance for early discontinuation of ultimately inefective treatment, preventing side efects for the patient, allowing earlier initiation of alternative treatment and reducing the costs associated with futile treatment. 4. A pharmaceutical is radiolabeled and imaged to assess pharmacokinetics (PK) and pharmacodynamics (PD). [van der Veldt et al. 2012]

Abstracts

For this indication it is very important that the compound is very little or preferably not at all afected by radiolabeling, thus truly relecting the biological characteristics of the unlabeled initial compound. Radiolabeling should not change the biodistribution, afect tissue penetration (e.g. altered blood-brain-barrier penetration) etc. Radiolabeled drugs provide insight in the actual accumulation in tumors and normal organs and allow correlation with physiological phenomena such as blood low.

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References Desar IM, Stillebroer AB, Oosterwijk E, Leenders WP, van Herpen CM, van der Graaf WT, Boerman OC, Mulders PF, Oyen WJ. 111In-bevacizumab imaging of renal cell cancer and evaluation of neoadjuvant treatment with the vascular endothelial growth factor receptor inhibitor sorafenib. J Nucl Med 2010; 51: 1707-15

2.

Herrmann K, Benz MR, Krause BJ, Pomykala KL, Buck AK, Czernin J. (18)F-FDG-PET/CT in evaluating response to therapy in solid tumors: where we are and where we can go. Q J Nucl Med Mol Imaging 2011; 55: 620-32

3.

Kam BL, Teunissen JJ, Krenning EP, de Herder WW, Khan S, van Vliet EI, Kwekkeboom DJ. Lutetiumlabelled peptides for therapy of neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2012; 39 Suppl 1: S103-12

4.

Oude Munnink TH, Nagengast WB, Brouwers AH, Schröder CP, Hospers GA, Lub-de Hooge MN, van der Wall E, van Diest PJ, de Vries EG. Molecular imaging of breast cancer. Breast 2009;18 Suppl 3: S66-73

5.

Sharkey RM, Goldenberg DM. Cancer radioimmunotherapy. Immunotherapy 2011 ; 3: 349-70

6.

Soloviev D, Lewis D, Honess D, Aboagye E. [(18)F]FLT: an imaging biomarker of tumour proliferation for assessment of tumour response to treatment. Eur J Cancer 2012; 48: 416-24

7.

Van der Veldt AA, Lubberink M, Bahce I, Walraven M, de Boer MP, Greuter HN, Hendrikse NH, Eriksson J, Windhorst AD, Postmus PE, Verheul HM, Serné EH, Lammertsma AA, Smit EF. Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: implications for scheduling of anti-angiogenic drugs. Cancer Cell 2012; 21: 82-91

Abstracts

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CME II: Radionuclide Therapy & Dosimetry

Abstracts

PRRT: New Approaches

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2a

ǚ The Genomics of Neuroendocrine Tumors: From Gnosis to Sunesis I. M. Modlin (New Haven) Educational Objectives: 1. To learn the necessary basic knowledge on the genomics underlying the development and progression of neuroendocrine tumors 2. To deine the network of neuroendocrine cells (interactome) and its relevance to the development of therapy, identifying druggable addiction points 3. To illustrate the basis of blood transcript analysis in diagnosis of NET disease and the potential role of molecular transcripts as a surrogate marker for the eicacy of PRRT Despite the signiicant improvement in knowledge of neuroendocrine tumors (NETs), the diagnosis of these lesions is typically delayed by at least 5–7 years after the onset of clinical symptoms, when the tumor has developed metastases or resulted in signiicant local invasion. The availability of sensitive and speciic plasma assays for peptides and amines produced by NET, and the development of immunohistochemical techniques, has resulted in a greater facilitation of diagnosis, both on blood and on tissue, while more sophisticated imaging techniques have greatly increased the identiication and staging of these diseases. A key unmet need therefore is the availability of a blood test for early diagnosis, identiication of covert metastases and as a surrogate for identifying eicacy of therapy. Current scientiic techniques have made it apparent that in neuroendocrine tumor cells there exists a complex genomic regulatory system (interactome) controlled by master regulator genes. These sustain the development and progression of NETs, and provide sites that are relevant to the development of (drone) therapy and in the identiication of druggable addiction points. Using a series of molecular genomic strategies it is now possible to speciically address key novel targets in an individual patient’s tumor and thus signiicantly alter the conceptual management of gastro-entero-pancreatic (GEP) NETs. A panel of genetic markers using microarray studies has been identiied and has been used to develop a classiication system for NET of the small intestine. This system has been successfully used to diferentiate the various subtypes of cancer and can accurately predict the presence of metastasis. The detection of CgA with Real-Time PCR is a much more sensitive than the conventional immunohistochemical and histochemical techniques to identify the presence of micrometastases. Nevertheless CgA remains a biomarker of considerable non speciicity and has limited application especially if examined using rigorous criteria.

Abstracts

PCR-based approaches aimed at studying diferent target genes can be used to more accurately deine the strategy of the management of patients. Indeed, as an alternative to analysis of tissues, the detection of circulating tumor-derived mRNA transcripts by PCR, alone or in combination with standard tests of detection of circulating peptides and amines, represents a new and highly accurate approach for the diagnosis of NETs. The identiication of a multi panel of NEN gene transcripts encoding gene regulators of cell proliferation, metastasis has allowed the development a predictive mathematical algorithm of exquisite sensitivity and speciicity to identify transcripts expressed in GEP-NETs. These can be identiied in the blood with a precision that enables the prediction of covert metastasis and facilitates the pathological characterization of NEN. Blood transcript analysis can be, therefore, used as a surrogate marker for the eicacy of PRRT as well as a predictor of disease status.

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References Drozdov I, Kidd M, Nadler B, Camp RL, Mane SM, Hauso O, Gustafsson BI & Modlin IM 2009 Predicting neuroendocrine tumor (carcinoid) neoplasia using gene expression proiling and supervised machine learning. Cancer 115 1638–1650

2.

Kidd M, Modlin IM, Mane SM, Camp RL & Shapiro MD 2006 QRT-PCR detection of chromogranin A: a new standard in the identiication of neuroendocrine tumor disease. Annals of Surgery 243 273–280

3.

Modlin IM, Gustafsson BI, Drozdov I, Nadler B, Pfragner R & Kidd M 2009 Principal component analysis, hierarchical clustering, and decision tree assessment of plasma mRNA and hormone levels as an early detection strategy for small intestinal neuroendocrine (carcinoid) tumors. Annals of Surgical Oncology 16 487–498

Abstracts

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2b

ǚ Dosimetry and Radiobiology for PRRT: Clinically Relevant or is it just a Physicist's Hobby? G. Flux (Sutton Surrey) Educational Objectives: 1. To review aspects of quantitative imaging for peptide receptor therapy 2. To review methods of absorbed dose calculations for peptide receptor therapy 3. To consider implications of radiobiology for peptide receptor therapy As evidence-based and personalised medicine become important for cancer treatment, including that with radiopharmaceuticals, PRRT is well placed to take advantage of this trend. Whilst molecular radiotherapy has conventionally been performed with empiric, ixed activities, possibly modiied according to patient weight or body surface area, there is now increasing evidence that the efect of treatment is dependent not on the activities administered to a patient, but to the distribution and retention of uptake of the administered agent. Quantitative imaging for PRRT is a pre-requisite for accurate internal dosimetry. This is more achievable for some radionuclides than for others. Lu-177, with a physical half life of 6.7 days is well suited to therapy as it emits beta particles for therapy and has a gamma emission of 203 keV which can be used for imaging. There is also justiication for administering Y-90, although bremstrahlung imaging is required which produces signiicantly poorer spatial resolution. Dosimetry in this case can be achieved either with a pre-therapy administration, for example with Ga-68 which has superior image quality but sufers from a short half-life, thereby preventing an efective half life to be ascertained, or with a pre-therapy, or concomitant administration of In-111 for imaging and dosimetry purposes. As In-111 has good imaging properties and a similar physical half-life to Y-90, this can be an ideal surrogate. There is abundant evidence that a range of absorbed doses are delivered from empiric administrations and there is increasing evidence of absorbed dose-efect correlations. Interest is now turning to radiobiological considerations, on the basis that as these govern administration schedules in external beam radiotherapy similar considerations should be applied to nuclear medicine. The Biological Efective Dose (BED) is a common method to take into account the dose rate, half-life and cellular repair times and could conceivably be used to inform optimal timings for interval treatments. It is likely that as PRRT becomes more accepted as a mainstream cancer treatment modality, the personalisation of treatment, based on quantitative imaging, internal dosimetry and radiobiology will enter routine practice rather than remain predominantly as a research tool. References Barone R, Borson-Chazot F, Valkema R et al Patient-Speciic Dosimetry in Predicting Renal Toxicity with 90Y-DOTATOC: Relevance of Kidney Volume and Dose Rate in Finding a Dose–Efect Relationship J Nucl Med 46:99S-106S 2005

2.

Hindorf C, Chittenden S, Causer L et al Dosimetry For 90Y-DOTATOC Therapies in Patients with Neuroendocrine Tumors Cancer Biother Radiopharm 22 (1) 2007

3.

Konijnenberg M, Melis M, Valkema R et al Radiation Dose Distribution in Human Kidneys by Octreotides in Peptide Receptor Radionuclide Therapy J Nucl Med 48:134-142 2007

4.

Cremonesi M, Ferrari M, Di Dia A et al Recent issues on dosimetry and radiobiology for peptide receptor radionuclide therapy Q J Nucl Med Mol Imaging. Apr;55(2):155-67 2011

Abstracts

1.

14

2c

ǚ PRRT: from the EANM – IAEA – SNM Guidance Document towards Standardization of Individualized Treatments L. Bodei (Milan) Educational Objectives:

EANM 13


1. To have an overview of the current status of clinical protocols of PRRT in neuroendocrine tumors 2. To learn the current advantages and limitations of PRRT 3. To illustrate the possibilities of personalized treatments Peptide Receptor Radionuclide Therapy (PRRT) consists of the systemic administration of a synthetic somatostatin analog, radiolabeled with a suitable beta-emitting radionuclide. The compound is able to irradiate tumors and their metastases via internalization through somatostatin receptors over-expressed on the cell membrane. As a result, the radiopharmaceutical is concentrated in the tumor cell, where sensitive molecules, such as DNA, can be targeted. In more than 15 years of academic phase I/II trials, despite the lack of homogeneity among studies, PRRT has proved to be eicient and consistent in eicacy and has, ultimately, demonstrated an impact on survival. Side efects of PRRT typically afect the kidneys and the bone marrow. These, however, are mild and self-limiting, provided adequate protective measures are undertaken. PRRT is generally well tolerated. Dosimetric studies indicated that it is possible to deliver elevated absorbed doses to the tumor, while limiting the dose to organs, such as kidneys and bone marrow, to tolerance limits. Despite the large body of evidence regarding eicacy and clinical safety – and practicability – of the ixed dose approach, PRRT still has gray zones of ineicient treatments due to the administration of inadequate absorbed doses to the target or excessive absorbed doses to normal organs. Current clinical protocols of PRRT, which are relected in the common document that has been written by experts reunited under the auspices of IAEA, EANM and SNMMI, include mainly empirical treatments or treatments based on the dose-limiting toxicity concept. Individualization, by means of dosimetry, for example, is considered time- and resource consuming. However, the capacity to respond to PRRT, as well as the susceptibility to possible detrimental efects, has an individual genetic basis. The lecture will give an overview on the current advantages and limitations of PRRT, will deine the parameters of standardization that can be regarded as milestones today, and will explore the possibility of going towards personalized treatments, capitalizing the input deriving from the biologic and dosimetric approaches.

Bodei L, Ferone D, Grana CM, Cremonesi M, Signore A, Dierckx RA, Paganelli G. Peptide receptor therapies in neuroendocrine tumors. J Endocrinol Invest 2009; Apr;32(4):360-9

2.

Kwekkeboom DJ, Kam BL, van Essen M, Teunissen JJ, van Eijck CH, Valkema R, de Jong M, de Herder WW, Krenning EP. Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors. Endocrine Rel Cancer 2010; Jan 29;17(1):R53-73

3.

Bodei L, Cremonesi M, Grana CM, Chinol M, Baio SM, Severi S, Paganelli G. Yttrium-labelled peptides for therapy of NET. Eur J Nucl Med Mol Imaging 2012; Feb;39 Suppl 1:S93-102

4.

Cremonesi M, Ferrari M, Di Dia A, Botta F, De Cicco C, Bodei L, Paganelli G. Recent issues on dosimetry and radiobiology for peptide receptor radionuclide therapy. Q J Nucl Med Mol Imaging 2011; Apr;55(2):155-67

15

Abstracts

References 1.


CME III: Physics

Abstracts

Motion Correction

16

3a

ǚ Principles of Motion Correction and Gating K. Thielemans (London) In many cases in medical imaging subject motion, either respiratory, cardiac or voluntary motion, is unavoidable. For instance, in diagnostic PET the acquisition duration is currently roughly 2 minutes per bed position. Motion during acquisition leads to blurring in the resulting (static) images. This may in turn lead to lower detectability of tumours, inaccurate SUV calculation, and incorrect lesion or planning volumes in radiation therapy. For emission imaging, in addition to blurring motion causes artefacts due to mismatch with the CT image used for attenuation correction. It can therefore be advantageous to detect (and even correct for) patient motion. For other applications the diferent motion states are of interest, for instance in cardiac studies to ind the ejection fraction and/or wall motion, or in radio-therapy planning.

EANM 13


For cardiac or respiratory motion, “gating” can be used to split the data into diferent motion states. Gating relies on the quasi-periodic motion and attempts to put data acquired during diferent parts of the motion cycle into diferent gates which are individually reconstructed. We will briely discuss diferent types of gating (e.g. phase, displacement or quiescent period gating) and their trade-ofs. The gates are determined based on information from external devices, such as a spyrometer or the chest position for respiratory movement, or an ECG signal for cardiac gating. Recent research to extract a gating signal out of the measured data is illustrated with example results. Using gated data, we can then study the inluence of motion during emission imaging and/or CT on the reconstructed images. Examples will be given using simulated and clinical data. The main disadvantage of gating is that each of the gated images is noisier than the static image. Motion correction attempts to overcome this by combining the gates into a single image, e.g. after image registration. Methods will be briely reviewed as tools are now becoming available to perform respiratory motion correction in clinical practice. References M. Dawood, F. Buether, N. Lang, O. Schober, and K. P. Schaefers, “Respiratory gating in positron emission tomography: A quantitative comparison of diferent gating schemes,” Medical Physics, vol. 34, no. 7, pp. 3067-3076, 2007. http://dx.doi.org/10.1118/1.2748104

2.

J. Fitzgerald and P. G. Danias, “Efect of motion on cardiac SPECT imaging: Recognition and motion correction,” Journal of Nuclear Cardiology, vol. 8, no. 6, pp. 701-706, Nov. 2001. http:// dx.doi.org/10.1067/mnc.2001.118694

3.

S. Nehmeh and Y. Erdi, “Respiratory motion in positron emission Tomography/Computed tomography: A review,” Seminars in Nuclear Medicine, vol. 38, no. 3, pp. 167-176, May 2008. http:// dx.doi.org/10.1053/j.semnuclmed.2008.01.002

4.

A. Rahmim, O. Rousset, and H. Zaidi, “Strategies for motion tracking and correction in PET,” PET Clinics, vol. 2, no. 2, pp. 251-266, Apr. 2007. http://dx.doi.org/10.1016/j.cpet.2007.08.002

5.

D. Visvikis, F. Lamare, P. Bruyant, N. Boussion, and C. Chezelerest, “Respiratory motion in positron emission tomography for oncology applications: Problems and solutions,” Nuclear Instruments and Methods in Physics Research Section A, vol. 569, no. 2, pp. 453-457, Dec. 2006. http://dx.doi. org/10.1016/j.nima.2006.08.153

Abstracts

1.

17


3b

ǚ Clinical Use of Cardiac Gating within PET and SPECT P. Knaapen (Amsterdam) Cardiac nuclear imaging with SPECT and PET are the most widely utilized techniques for the evaluation of myocardial perfusion and viability in the clinical work-up of patients suspected of or with known coronary artery disease (CAD). With the introduction of ECG-gated image acquisition, the diagnostic and prognostic information obtained from such studies have been signiicantly enhanced.1 Gated acquisition allows for accurate, automated, and reproducible assessment of global left ventricular (LV) dimensions and function, as well as regional wall motion abnormalities (RWMA). These parameters have shown to provide incremental value over perfusion or metabolic imaging alone.2 For example, evaluation of RMWA and thickening in the presence of a ixed perfusion defect aids in the discrimination between a soft attenuation artefact from an actual defect due to myocardial scar or dysfunctional but potentially viable myocardium. Therefore, the number of false positive scans are substantially reduced, particularly in women and obese patients in whom attenuation artefacts are relatively common. Next to the well documented prognostic value of resting LV ejection fraction (LVEF), the assessment of post stress LVEF further facilitates the interpretation of a study.3 An appreciable reduction of post stress LVEF due to persistent LV dysfunction, mediated through myocardial stunning, is linked to the extent and severity of CAD. Moreover, an apparent normal perfusion study in the presence of balanced ischemia may be unmasked by a reduction of post stress LVEF. Within the context of a gated study, evaluation of RMWA may also assist in the assessment of myocardial viability (recovery of RMWA) and ischemia (induction of RMWA) during low and high dose inotropic stimulation, respectively. More recently, phase analysis of gated acquisitions have enabled to detect LV mechanical dyssynchrony is patients with dilated cardiomyopathy and left bundle branch block.4 The presence of LV dyssynchrony not only serves as a prognostic marker in patients with heart failure, but may also guide clinical management regarding the eligibility for cardiac resynchronization therapy (CRT). Although gated imaging has improved nuclear cardiac imaging, one should be aware of potential inaccuracies due to irregular heart rhythm, small LV dimensions, large myocardial defects, and extra cardiac activity. Finally, it needs to be emphasized that estimated LVEF obtained with alternative imaging modalities (e.g. echocardiography, CMR, or CT) are generally not interchangeable.5

Abstracts

References 1.

Sciagra R. The expanding role of left ventricular functional assessment using gated myocardial perfusion SPECT: the supporting actor is stealing the scene. Eur J Nucl Med Mol Imaging 2007;34:1107-1122

2.

Lima RS, Watson DD, Goode AR et al. Incremental value of combined perfusion and function over perfusion alone by gated SPECT myocardial perfusion imaging for detection of severe threevessel coronary artery disease. J Am Coll Cardiol 2003;42:64-70

3.

Johnson LL, Verdesca SA, Aude WY et al. Postischemic stunning can afect left ventricular ejection fraction and regional wall motion on post-stress gated sestamibi tomograms. J Am Coll Cardiol 1997;30:1641-1649

4.

Chen J, Garcia EV, Folks RD et al. Onset of left ventricular mechanical contraction as determined by phase analysis of ECG-gated myocardial perfusion SPECT imaging: Development of a diagnostic tool for the assessment of cardiac mechanical dyssynchrony.J Nucl Cardiol 2005;12:687-95

5.

Bellenger NG, Burgess MI, Ray SG et al. Comparison of left ventricular ejection fraction and volumes by echocardiography, radionuclide ventriculography and cardiovascular magnestic resonance. Are they interchangeable? Eur Heart J 2000;21:1387-1396

18

3c

ǚ 4D PET/CT for Radiotherapy Treatment Planning D. Thorwarth (Tuebingen) The aim of this lecture is to review state of the art techniques for the integration of 4D PET/CT data into radiotherapy (RT) treatment planning (TP). First, the efects of breathing motion on the acquisition of PET/CT data will be discussed in addition to diferent currently available techniques for the assessment of breathing patterns and tumor motion. Furthermore, diferent concepts for reconstructing 4D PET/CT data will be reviewed (phase-based, intensity-based).

EANM 13


For the integration of 4D PET/CT imaging data into RT TP, diferent strategies for tumor volume delineation have been proposed recently and will be discussed during this lecture, such as the internal target volume (ITV) concept or the deinition of a gross tumor volume (GTV) based on PET data acquired during free breathing or maximum intensity projection (MIP) PET data. In a last part of the presentation, several methodological approaches for the integration of 4D imaging data into the dose planning and optimization process during RT TP will be reviewed and critically discussed. References Bettinardi V, Picchio M, Di Munzio N, Gianolli L, Gilardi MC, Messa C. Detection and compensation of organ/lesion motion using 4D-PET/CT respiratory gated acquisition protocols. Radiother Oncol 2010; 96(3): 311-6.

2.

Van Elmpt W, Hamill J, Jones J, De Ruysscher D, Lambin P, Ollers M. Optimal gating compared to 3D and 4D PET reconstruction for characterization of lung tumours. Eur J Nucl Med Mol Imaging 2011; 38(5): 843-55.

3.

Callahan J, Kron T, Schneider-Kolsky M, Dunn L, Thompson M, Siva S, Aarons Y, Biuns D, Hicks RJ. Validation of a 4D-PET Maximum Intensity Projection for Delineation of an Internal Target Volume. Int J Radiat Oncol Biol Phys 2013; (epub). Doi: 10.1016/j.ijrobp.2013.02.030.

4.

Söhn M, Weinmann M, Alber M. Intensity-modulated radiotherapy optimization in a quasi-periodically deforming patient model. Int J Radiat Oncol Biol Phys 2009; 75: 906-14.

5.

Aristophanous M, Berbeco RI, Killoran JH, Yap JT, Sher DJ, Allen AM, Larson E, Chen AB. Clinical utility of 4D FDG-PET/CT scans in radiotherapy treatment planning. Int J Radiat Oncol Biol Phys 2012; 82(1): e99-105.

Abstracts

1.

19


CME IV: Radiopharmacy & Drug Development

Abstracts

State of the Art of Radiopharmaceuticals

20

4a

ǚ New SPECT Tracers R. Schibli (Zurich) SPECT and planar scintigraphy are still important imaging modalities in nuclear medicine. Despite this fact, only a few new SPECT tracers have reached market approval in the last years. Thus, the question can be raised: is there a future for SPECT tracers? We believe that there is for the following reasons: i) Infrastructure costs to produce PET-tracer are far more expensive than for e.g. 99mTc- or 111In- and 123I-tracers. Even generator systems for PET radiometals (e.g. 68Ge/68Ga) are expensive particularly in GMP quality; ii) Half-lives of most PET radionuclides including 68Ga are short. Hence, logistics from lab-to-patient are diicult and quickly become commercially unattractive. Radionuclides approved for SPECT are less expensive and have longer half-lives; iii) The density of clinical center possessing PET/CT scanners in Europe is extremely high. In developing and emerging countries this is not the case. Consequently SPECT and SPECT tracers remain an important pillar for patient management in these countries. iv) Pre-clinically SPECT scanners are already outperforming commercial PET/CT scanners in terms of spatial resolution1. Spatial resolution of clinical SPECT scanners have improved as well; Considering these points, the development of new and novel SPECT tracer is still attractive and important. In the last years, several molecular targets have been identiied, which are attractive SPECT and radionuclide therapy. Encouraging data of phase 1 studies using 99mTc- and 123I-radiolabeled molecules targeting the prostate-speciic membrane antigen have recently been published 2. Several clinical studies of new 99mTc-labeled vitamin derivatives (folic acid and B12) for detection of cancer and inlammation showed promising results with respect to speciic targeting and in vivo clearance characteristics 3. Novel bone seeking agents labeled with 99mTc and 188Re and 111In-labeled minigastrin analogues (targeting the CCK-2 receptors) are close to clinical testing 4. Furthermore, novel 99mTc-labeling methodologies such as the 99mTcVII-trioxo core have been invented 5. New radiolanthanides with attractive decay properties such as 155Tb (T1/2 = 5.32 d; Egamma = 105 keV) have been successfully assessed in vivo 6. This presentation will give an overview of the latest trends in chemical, pre-clinical and clinical SPECT tracer developments, their potential and limitations.

EANM 13


References Deleye et al. Eur J Nucl Med Mol Imaging. 2013;40:744-58

2.

Hillier et al. J Nucl Med 2011;52:1087-93; Barrett et al. J Nucl Med 2013; in press; 1.Kularatne et al. Mol Pharm 2009;6:790-800

3.

Vaitilingam et al. J Nucl Med 2012; 53:1127-34.; Matteson et al. Clin Exp Rheumatol. 2009; 27:2539; Sah et al. submitted

4.

Torres et al. Bioconjug Chem 2010; 21:811-5; Laverman et al. Eur J Nucl Med Mol Imaging 2011; 38:1410-6

5.

Braband et al. Chemistry 2009;15:633-8

6.

Müller et al. J Nucl Med 2012;53:1951-9

Abstracts

1.

21


4b

ǚ New Radiopharmaceuticals for PET P. H. Elsinga (Groningen) PET is a cost-efective tool in therapy evaluation and can largely contribute to the growing need for personalized medicine. Currently [18F]luoro-deoxyglucose (FDG) is the workhorse of PET and is abundantly applied in the detection of primary tumors and metastases. To optimally utilize PET in therapy evaluation, more suitable validated tracers beyond FDG are required. An ever-increasing number of newly discovered biological targets is available for study since the recent publication of the human genome. However, the repertoire of well-characterized PET radiotracers for in vivo imaging is limited. The development of new PET imaging probes relies mainly on the radionuclides 11C and 18F. However other useful PET-radionuclides are emerging such as 64Cu, 68Ga, and 89Zr. These radionuclides have their speciic characteristics with respect to half-life, positron energy (resolution), positron abundance and availability. Depending of the biological target of interest and the properties of the PET-radiopharmaceutical the proper radionuclide should be selected. Most of these synthetic routes for 11C are based on 11C-methylation reactions. Well-known examples of these PET-radiopharmaceuticals are 11C-raclopride, 11C-choline and 11C-PIB. An interesting new development is based on 11C-carbon monoxide1. For 18F-radiopharmaceuticals there is still a need to simplify 18F-chemistry to allow better dissemination of PET. Standard [18F]luorination productions involve nucleophilic substitutions by azeotropically dried [18F]luoride, often followed by a luoroalkylation or a hydrolysis step. Finally, puriication and formulation steps are needed. Examples of such production methods are FDG, FLT and FAZA. New methodology has been developed (click chemistry2, conjugation to peptides3) to further extend the number of 18F-radiopharmaceuticals. Metal-based PET-radionuclides such as 64Cu, 89Zr and 68Ga are increasingly used thereby building on the long-lasting experience that the community gained with SPECT-radiopharmaceuticals. These radionuclides are mainly being used for radiolabelling of peptides, proteins and antibodies. Since 64Cu and 89Zr have a relatively long half life they may easily be distributed over long distances and can be used to produce a wide range of peptides and antibodies. 89Zr has been applied to a number of monoclonal antibodies that are conjugated with a desferal chelating group. 89Zr-labelled monoclonal antibodies allow PET scanning up to 7 days, where usually maximal target over non-target ratio is being reached at 3–4 days post injection4. Recenty, 68Ga has become available through a GMP-compliant generator and is very suitable to produce radiolabelled peptides5. In conclusion, several new labeling techniques have resulted in new PET-radiopharmaceuticals. References Eriksson J, Windhorst AD. J Lab Compd Radiopharm 54, S24 (2011)

2.

Campbell-Verduyn LS, Mirfeizi L, Schoonen AK, Dierckx RA, Elsinga PH, Feringa BL. Angew Chem Int Ed Engl. 50, 11117-11120 (2011)

3.

McBride WJ, D'Souza CA, Sharkey RM, Goldenberg DM. Appl Radiat Isot. 70, 200-204 (2012)

4.

Van Dongen GA, Vosjan MJ. Cancer Biother Radiopharm. 25, 375-385 (2010)

5.

Prata MI. Curr Radiopharm. 5, 142-149 (2012)

Abstracts

1.

22

4c

ǚ New Radiopharmaceuticals for Therapy G.-J. Meyer (Hannover) Nuclear medicine has two aspects of activity, namely diagnostics and therapy. Whereas the diagnostic part is always in strong competition with new modalities like MRI, the therapeutic part ofers new ields of applications beyond the classic strategies. Targeted radio(immuno)therapy ofers discrete and efective cellular destruction options with minimal systemic side-efects. The classical approach towards thyroid malignancies with iodine-131 has recently been extended by the use of radiolabelled regulatory peptides to target endocrine tumours. The success story of somatostatine derivatives labelled with Y-90 and Lu-177 for PRT (Peptide Receptor Therapy) has newly triggered the development of further similar radiopharmaceuticals.

EANM 13


Key requirement for such strategies is the knowledge of peptide ainities towards malignant cell lines. Malignant cell lines of special tumour types may behave similar, however it seems to be an illusion to ind the individual personalized target structures for each patient. Targeting vectors may be subclassiied in four categories: antibodies, antibody fragments down to diabodies, peptides, and smaller molecules. In therapeutic applications it is important to tag the target-organ fast in order to minimize the radiation burden to the rest of the body. Since antibodies exhibit relatively long systemic circulation times, pretargeting strategies are anticipated, using either biotin-streptavidine coupling, or in situ click-chemistry. Antibody fragments have shorter circulation times so that they may be used as labelled vectors directly. Peptides have been shown to reach their targets fast and are the most promising candidates for new radiopharmaceuticals. Examples of promising target vectors include bombesin-derivatives, gastrin-derivatives, and RGD-peptide derivatives. Smaller molecule examples include amino acids and even inorganic molecules. In order to maximize the therapeutic eicacy of targeting vectors it has been anticipated, that cell-internalization would be a necessary prerequisite. Therefore agonist-vectors were the only candidates for therapy approaches. Recently it was shown, however, that antagonists might be useful candidates also, although they are not internalized. Depending on the radionuclide to be coupled to the vectors, the cellular damage may be enhanced by cross-ire efects and hitherto not fully understood phenomena, as e.g. the bystander-efect. Using high-energy beta emitters and high LET-alpha emitters the internalization requirement may not be a necessary prerequisite. Additionally the choice of an adequate radionuclide for certain tumour entities plays an essential role in the development of radiopharmaceuticals for therapy. In the future the individual tumour pathology like typology, site and position, size, vascularisation, necrosis, metastatic-status and other factors may require a personalized choice of radionuclide to label the vector.

Recently alpha-emitters have come into focus for therapeutic applications again: among the promising candidates are Ra-223, Bi-213, and At-211, with the latter one being the only nonmetal radioisotope.

23

Abstracts

All promising β-emitters are metal cations with hallives in the range of 2 to 6 days. The max. β-energies range from ca. 0.5 MeV (e.g. Cu-67) to ca. 2.3 MeV (e.g. Y-90). Although nearly 100 radioisotopes with these characteristics are known, the main requirement for the application is the commercial availability of the isotope. This limits the choice of radioisotopes to about 10–15. Ideally the isotope emits γ-rays additionally in order to allow the follow-up of the distribution of the agent. Alternatively α positron emitting short-lived isotope of the element is available to determine the biodistribution. These cationic radionuclides are usually coupled to the vectors by chelating agents, most often of nitrogen-crown type. Using diferent types of spacers, the biokinetic behaviour may be adjusted. In special cases Auger-emitters have been considered as therapeutically useful radioisotopes also. Because of their very short active range, these should be considered only for vectors, which are internalized in the target cells.


CME V: Cardiovascular

Abstracts

Myocardial Viability

24

5a

ǚ Critical Appraisal of Viability Assessment H.J. Verberne (Amsterdam) Patients with multi-vessel coronary artery disease (CAD) in combination with complex coronary artery anatomy, and/or associated left ventricular (LV) impairment are at a high risk of complications related to revascularization procedures. However especially these high risk patients tend to beneit the most from revascularisation. Therefore appropriate patient selection is crucial and should be based on an accurate assessment of both possible risks and beneits. Important parameter in this setting is the presence of myocardial viability i.e. dysfunctional but potentially viable myocardium (“stunned or hibernating myocardium”). Stunning is deined as reversible contractile dysfunction in the presence of restored coronary blood supply, following a brief period of coronary occlusion 1, 2. Contractile recovery in this acute “stunned” state may occur spontaneously many weeks to months after restoration of a normal blood supply to the previously ischemic myocardium 2. In contrast, hibernating myocardium has been deined as a state of down-regulated contractile function in non-infarcted myocardium in the setting of severe coronary stenosis that improves after revascularisation1, 2.

EANM 13


The assessment of myocardial viability has been an important prerequisite in the decisionmaking regarding revascularisation. This central role of myocardial viability assessment was supported by observational studies and meta-analyses showing that after revascularization patients with myocardial viability had a better outcome compared to those without myocardial viability 3. However with the publication of the STICH (Surgical Treatment for Ischemic Heart Failure) trial 4 and especially the viability sub-study 5, questions have arisen regarding the beneit of viability testing in patients with left ventricular systolic dysfunction and CAD prior to revascularization decisions. The main criticism is that the STICH-study was not designed for the assessment of the beneit of viability testing in a randomised way. Therefore the indings that suggest that viability testing may not be the only or most important independent determinant of outcome should be viewed with some caution.

Abstracts

Acknowledging that prospective outcome data are limited, viability testing still has a role in complex patients who are at the highest risk of adverse events from revascularization. In this scenario an objective measurement of viability can tip the balance in favour of medical therapy or revascularization. Myocardial viability testing will continue to play a role in revascularisation decision making, although larger randomised trials with clinical outcome end-points are needed to further deine its role 6–8.

25


References Heyndrickx GR, Baig H, Nellens P, Leusen I, Fishbein MC, Vatnerm SF. Depression of regional blood low and wall thickening after brief coronary occlusions. Am J Physiol 1978; 234: H653–H659

2.

Braunwald E, Kloner RA. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation 1982; 66:1146–1149

3.

Allman KC, Shaw LJ, Hachamovitch R, Udelson JE. Myocardial viability testing and impact of revascularization on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis. J Am Coll Cardiol 2002; 39:1151–1158

4.

Velazquez EJ, Lee KL, Deja MA, STICH Investigators et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med, 364 (2011), pp. 1607–1616

5.

Bonow RO, Maurer G, Lee KI, STICH Investigators et al. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med 2011; 364:1617–1625

6.

Grover S, Srinivasan G, Selvanayagam JB. Myocardial viability imaging: Does it still have a role in patient selection prior to coronary revascularisation? Heart, Lung and Circulation 2012; 21:468– 479

7.

Mc Ardle BA, and Beanlands RS. Myocardial Viability: Whom, what, why, which, and how? Can J Cardiol 2013; 29:399-402

8.

Chareonthaitawee P, Gersh BJ, Panza JA. Is viability imaging still relevant in 2012? J Am Coll Cardiol 2012; 5:550-558

Abstracts

1.

26

5b

ǚ SPECT and PET/CT Assessment C. Übleis (Munich) Non-invasive nuclear measurement of viability remains a cornerstone in the diagnostic of coronary artery disease (CAD), an important factor regarding the developement of (chronic) heart failure (HF). In contrast to other non-invasive tools, SPECT and PET are able to provide information about the molecular processes themselves regarding viability, perfusion and innervation. Furthermore these techniques are not hampered by implanted devices and they enable – as far as possible – a user independent (automated) data acquisition and analysis.

EANM 13


The method was strengthened in recent years by the introduction of hybrid PET/CT and SPECT/CT scanners, enabling anatomical localization and attenuation correction, as well as by the marketabillity of specialized cardiac SPECT camera-systems using a cardio-centric geometry combined with ultra-high-sensitive detectors. Myocardial perfusion imaging (MPI) is still the most conducted nuclear application in CAD and/ or HF patients 1 due to a wide spread availability of cameras and tracers. The established tracers for the identiication of viable myocardium are 201Tl, 99mTc-Sestamibi and 99mTc-Tetrofosmin. Despite the disadvantage of high radiation dose of 201Tl, it allows detection of myocardial viability according to the fact, that its late phase of uptake depends on the function of the sarcolemmal membrane. 99mTc compounds allow a higher image resolution and also an ECG-gated image acquisition. Due to their lipophilicity Sestamibi and Tetrofosmin cross the plasma membrane and are trapped in viable mitochondria. Therefore the tracers can be used to identify both myocardial perfusion and viability. F-FDG PET imaging relects the glucose uptake of the cardiomyocytes and is regarded as the golden standard of cardiac viability dignostics.2 But the tracer-uptake is mainly inluenced by metabolic status so that a glucose loading protocol or a hyperinsulinemic euglycemic clamping is necessary to maximize glycolysis and myocardial uptake. The combination of rest MPI and 18 F-FDG PET is generally accepted to diferentiate between scar (no perfusion, no FDG-uptake), viable myocardium (perfusion and FDG-uptake) and mismatch (no perfusion but FDG-uptake). The latter – known as hibernating myocardium – predicts at 5% to 7% threshold a superior outcome when revascularized successfully. 3, 4 18

Beside this background information, the presentation will include common protocols for the above mentioned tracers and examinations.

1.

Hendel RC, Berman DS, Di Carli MF, Heidenreich PA, Henkin RE, Pellikka PA, Pohost GM, Williams KA. Accf/asnc/acr/aha/ase/scct/scmr/snm 2009 appropriate use criteria for cardiac radionuclide imaging: A report of the american college of cardiology foundation appropriate use criteria task force, the american society of nuclear cardiology, the american college of radiology, the american heart association, the american society of echocardiography, the society of cardiovascular computed tomography, the society for cardiovascular magnetic resonance, and the society of nuclear medicine. J Am Coll Cardiol. 2009;53:2201-2229

2.

Ghosh N, Rimoldi OE, Beanlands RS, Camici PG. Assessment of myocardial ischaemia and viability: Role of positron emission tomography. Eur Heart J. 2010;31:2984-2995

3.

D'Egidio G, Nichol G, Williams KA, Guo A, Garrard L, deKemp R, Ruddy TD, DaSilva J, Humen D, Gulenchyn KY, Freeman M, Racine N, Benard F, Hendry P, Beanlands RS. Increasing beneit from revascularization is associated with increasing amounts of myocardial hibernation: A substudy of the parr-2 trial. JACC Cardiovasc Imaging. 2009;2:1060-1068

4.

Di Carli MF, Davidson M, Little R, Khanna S, Mody FV, Brunken RC, Czernin J, Rokhsar S, Stevenson LW, Laks H, et al. Value of metabolic imaging with positron emission tomography for evaluating prognosis in patients with coronary artery disease and left ventricular dysfunction. Am J Cardiol. 1994;73:527-533

27

Abstracts

References


5c

ǚ Cardiac Magnetic Resonance Assessment M. Lombardi (Pisa) Cardiac Magnetic Resonance (CMR) is a very versatile imaging technique for the assessment of patients with left ventricular dysfunction. Indeed it combines the ability to assess left ventricular morphology and global and regional cardiac function and perfusion at rest and during stress with the capability to identify replacement of normal myocytes by ibrosis or necrosis in the hearts in characteristic patterns for ischemic as well as non-ischemic cardiomyopathies. Therefore it has become a central method for characterizing the etiology of LV dysfunction 1. Unlike echocardiography, the technique is also very robust and allows high quality imaging of the heart irrespective of the morphology of the thorax and of echocardiographic windows. It also has signiicantly better spatial and temporal resolution than nuclear imaging techniques. Several diferent CMR imaging techniques may be used, either individually, but most often combined in a comprehensive imaging protocol 2 which can be performed within approximately 20–30 minutes. The evaluation of myocardial thickness and of regional and global wall motion kinetics of the left ventricle on cine images alone can be a sign of myocardial viability alone. Indeed wall thinning less than 6 mm and aneurismal motion are morphological sign of transmural necrosis 3 in chronic infarcts as conirmed by histopathology. The correlation between metabolic activity and diastolic thickness in akinetic segments resulted wide/broad but signiicant (r=.48), and 44% of the segments resulted vital at PET. Reduced diastolic thickness has particular high negative predictive value of 90% to predict absence of recovery of function after revascularization 4. Similar to dobutamine MR, low dosage of Dobutamine (10–20 microg/min) is used to detect functional reserve in the case of viable tissue. Considering PET as the gold-standard, sensitivity and speciicity of dobutamine MRI for the diagnosis of myocardial viability have resulted to be respectively 81 and 95% with an 86% agreement. Late (LE) or delayed contrast enhancement (DE) imaging consist of the acquisition of T1 weighted images late (i.e 10–20 minutes after the administration of Gd based contrast medium. This technique allows to identify the presence of ibrotic tissue as well as of acutely or necrotic infarcted myocardium, because in such tissue, the volume of distribution to the extravascular contrast agent is increased and inlow and outlow kinetics are reduced, leading to higher concentration of the contrast agent late (10–20 minutes) after contrast injection in the infarcted compared to the normal myocardium. By using an “ad hoc” acquisition pulse sequence the infarcted region appear strongly hyperintense with extremely high contrast to produce a net distinction between necrotic and vital tissue 5. Because of high spatial resolution (1–2 mm), the technique allows to identify minute quantities of ibrotic or scarred tissue in the heart with excellent agreement against histopathology 6. Compared with this technique, sensitivity and speciicity of late hyperintensity result to be respectively 0.86 and 0.94. Similar results can be obtained comparing the results with 99mTCtetrofosmina G-SPECT7.

Abstracts

There is a relation between transmural extension of hyperenhancement and the recovery of contractile function after coronary revascularization 8. The chance of recovery decreases progressively with the transmural extention of late hyperintensity, since the average value of the latter is 10±7% in the segments that recover and 47±14% in the segments that don’t recover contractile function. CMR was also shown to be able to predict response to CRT diferentiating between non ischemic and ischemic cardiomyopathy Indeed CRT response of patients with ischemic cardiomyopathy appears to be worse than in patients with non ischemic cardiomyopathy. Furthermore DE-CMR may allow to precisely delineate the presence and the location of ibrosis avoiding to place left ventricular leads in necrotic areas and in particular when the scar is located in the posterolateral area 9.

28

References Mahrholdt H, Wagner A, Judd RM, Sechtem U, Kim RJ.: Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J. 2005;Aug;26(15):1461-74

2.

Hendel RC, Patel MR, Kramer CM et Al ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American College of Radiology, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Angiography and Interventions, and Society of Interventional Radiology. J Am Coll Cardiol 2006; 48(7):1475–1497

3.

Roberts CS, Maclean D, Maroko P, Kloner RA Early and late remodeling of the left ventricle after acute myocardial infarction. Am J Cardiol 1984;54: 407-410

4.

Baer FM, Theissen P, Schneider CA et Al. Dobutamine magnetic resonance imaging predicts contractile recovery of chronically dysfunctional myocardium after successful revascularization. J Am Coll Cardiol 1998;31: 1040-1048

5.

Fieno DS, Kim RJ, Chen EL, et Al. Contrast-enhanced magnetic resonance imaging of myocardium at risk: distinction between reversible and irreversible injury throughout infarct healing. J Am Coll Cardiol; 2000; 36; 1985-1991

6.

Kim RJ, Fieno DS, Parrish TB, Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 1999;100:1992-2002

7.

Giorgetti A, Pingitore A, Lombardi M et Al Quantitative evaluation of trasmural extent of myocardial necrosis by means of contrast-enhanced magnetic resonance: comparison with nitrate 99mTc-tetrofosmin G-SPECT scintigraphy. J Nucl Med 2002;46:4:92

8.

Kim RJ, Wu E, Rafael A, et Al. The use of contrast enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med; 2000;343: 1445-1453

9.

Bleeker GB, Kaandorp TA, Lamb HJ, et Al. Efect of posterolateral scar tissue on clinical and echocardiographic improvement after cardiac resynchronization therapy. Circulation. 2006 Feb 21;113(7):969-76

Abstracts

1.

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29


5d

ǚ Multimodality Interpretation and Comparison T. H. Schindler (Baltimore) With an increasing aging population, there is a continuous increase of heart failure manifestation due to coronary artery disease (CAD), which confers an unfavorable clinical outcome. Restoration of coronary low to ischemic-compromised but viable myocardium (so called hibernating-stunning myocardium) may improve symptoms, quality of life, and prognosis in these high-risk cardiomyopathy (CMP) patients. Thus, an accurate identiication and characterization of hibernating myocardium is critical for the decision-making process. Several imaging modalities exist for identifying hibernating myocardium in territories with contractile dysfunction in CMP patients. Choosing the best imaging modality for a speciic patient can be challenging. Current methods available for assessing viability include nuclear imaging with single photon emission tomography (SPECT) and positron emission tomography (PET), cardiac magnetic resonance (CMR), cardiac computed tomography (CT), and echocardiography. The efectiveness of these various imaging techniques in the assessment of myocardial viability, their strength and weaknesses will be reviewed and discussed. References Bonow RO, Maurer G, Lee KL, et al. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med 2011;364:1617-25

2.

Ghosh N, Rimoldi OE, Beanlands RSB, Camici PG. Assessment of myocardial ischaemia and viability: role of positron emission tomography. Eur Heart J (2010) 31, 2984–2995

3.

Partington SL, Raymond Y. Kwong RY, Dorbala S. Multimodality imaging in the assessment of myocardial viability. Heart Fail Rev (2011) 16:381–395

Abstracts

1.

30

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CME VI: Bone & Joint

Abstracts

The Limping Patient – Multimodality Imaging

31


6a

ǚ Unexplained Hip Pain H. K. Mohan (London) Evaluation of a limping patient needs careful clinical examination of the lower limbs and the spine and judicious use of imaging techniques to ascertain the origin of pain. Pain originating from the hip is one of the common causes of a limp in patients. The hip is a stable, major weightbearing joint with signiicant mobility. Hip pain has diferent aetiologies including bone, articular and soft tissue pathologies. Hip pain is experienced by more than 40% of adults over age of 65. However only 15% of older adults self report hip pain. 5–10% of athletes report hip pain annually. In the work-up of hip pain, the irst fact to establish is whether pain is felt in the anterior, lateral, or posterior part of the hip. Each location suggests a distinctive set of possible underlying causes. Imaging plays a vital role in the diagnosis and management of a signiicant number of these patients. Bone scintigraphy is a highly sensitive technique which has been used for more than four decades in the management of hip pain. In this CME presentation we look at the aetio-pathogenesis of hip pain, identify red lag symptoms requiring further investigations and discuss the various imaging techniques. We speciically look at the role of bone scintigraphy and SPECT/CT in this scenario with speciic case studies. References Margo K, et al. Evaluation and management of hip pain: An algorithmic approach J Fam Pract. 2003, 52:8

2.

Newberg AH, Newman JS. Imaging the painful hip. Clin Orthop Relat Res. 2003 Jan;(406):19-28

3.

Cobb JP, Davda K, Ahmad A, Harris SJ, Masjedi M, Hart AJ. Why large-head metal-on-metal hip replacements are painful: the anatomical basis of psoas impingement on the femoral head-neck junction. J Bone Joint Surg Br. 2011 Jul; 93(7):881-5.

4.

Erb RE. Current concepts in imaging the adult hip.Clin Sports Med. 2001 Oct; 20(4):661-96.

5.

Hedger S, Darby T, Smith MD. Unexplained hip pain: look beyond the obvious abnormality. Ann Rheum Dis. 1998 Mar; 57(3):131-3.

6.

Cuckler JM. Unexplained pain after THR: what should i do? Orthopedics. 2010 Sep 7;33(9):648

Abstracts

1.

32

6b

ǚ SPECT/CT in Knee Joints – What is Left for Nuclear Medicine Tests at the Era of MRI? K. Strobel (Luzern) MR is generally considered the imaging modality of choice for the evaluation of the knee joint because of the excellent visualization of important structures like ligaments, tendons, cartilage, menisci, bone marrow. Contraindications for MR (pacemaker, severe claustrophobia..) and metalic implants around the knee often hamper successfull MR imaging. SPECT/CT provides important metabolic and morphologic information and is increasingly available and used to evaluate patients with knee pain. Several studies showed the usefullness of SPECT/CT in the evaluation of knee prothesis 1–3. Buck et al. demonstrated that increased tracer uptake in bone scintigraphy is more sensitive for medial knee pain than bone marrow edema on MR 4. Osteoarthritis, osteomyelitis, osteochondral defects, osteoid osteoma or therapy response assessment after osteotomies are further examples of proper indications for SPECT/CT. The comparibility with the contralateral side and the possible combination with a whole body scintigraphy to exclude multifocal bone disease are additional advantages of SPECT/CT compared with MR. First case reports describe the combination of CT arthrography and SPECT/CT, called “SPECT/CT arthrography” delivering additional information about the cartilage and loose bodies in one investigation 5.

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In conclusion, SPECT/CT of the knee ofers promising combined metabolic/morphologic information for patients with knee pain. Literature is still limited but one can expect that SPECT/CT will play an increasing and important role in a variety of indications. References Hirschmann MT, Iranpour F, Davda K, Rasch H, Hugli R, Friederich NF. Combined single-photon emission computerized tomography and conventional computerized tomography (SPECT/CT): clinical value for the knee surgeons? Knee Surg Sports Traumatol Arthrosc. Mar;18(3):341-345.

2.

Hirschmann MT, Konala P, Iranpour F, Kerner A, Rasch H, Friederich NF. Clinical value of SPECT/CT for evaluation of patients with painful knees after total knee arthroplasty – a new dimension of diagnostics? BMC Musculoskelet Disord.12:36.

3.

Strobel K, Steurer-Dober I, Huellner MW, Veit-Haibach P, Allgayer B. [Importance of SPECT/CT for knee and hip joint prostheses]. Der Radiologe. Jul 2012;52(7):629-635.

4.

Buck FM, Hofmann A, Hofer B, Pirrmann CW, Allgayer B. Chronic medial knee pain without history of prior trauma: correlation of pain at rest and during exercise using bone scintigraphy and MR imaging. Skeletal radiology. Apr 2009;38(4):339-347.

5.

Strobel K, Wiesmann R, Tornquist K, Steurer-Dober I, Muller U. SPECT/CT arthrography of the knee. Eur J Nucl Med Mol Imaging. Dec 2012;39(12):1975-1976.

Abstracts

1.

33


6c

ǚ Foot Pain Unexplained by X-rays F. Paycha (Paris) Foot pain causing limping is a common clinical presentation that may account for 20% of caseload referrals for a bone scintigraphy 1. Foot bone and joint pain may be related to a mechanical condition (eg stress fracture), owing to body weightbearing, or a irst sign of a non-micro-traumatic disease (eg chronic rheumatic disease, osteomyelitis, avascular necrosis,…)1. Patient should be irstly asked by the Nuclear Medicine physician about the location and extent of pain to be consigned on a standardized anatomical scheme. The foot is a perfect marriage of form and function. The foot contains 26 bones, 2 sesamoid bones, 33 joints, 19 muscles and 107 ligaments assembled in a complex 3 D architecture. Because of this complex pedal skeleton, numerous variant accessory bones, hind-foot bones spongious dominant structure, foot lesions are regularly overlooked by plain X-rays and even often missed by MDCT. Therefore, bone scintigraphy plays a pivotal role in identifying causative lesions of a disabling pain left unelucidated by irst line morphological examinations. However, accurate localization of foot pathology on planar bone scans was challenging in the past. Indeed, the inherent problem of spatial resolution, in addition to the large number, the smallness (1st metatarsal width = 15 mm) and superimposition of the bones and extra-osseous structures of the foot, make diicult to separate the bones and because of shine-through of activity to show the exact sites and delineations of lesions on standard spot views. Bone SPECT/CT modality obviates most of the planar modality drawbacks 2. SPECT/CT acquisition parameters dedicated to lower limb extremities is a prerequisite to a reliable and fully eicient examination 3. Patient is lying supine with feet non-painful contention aids. The delayed SPECT acquisition typically includes 128x128 matrix, 64 step-and-shoot, 30s duration frames. Reconstruction is performed through OSEM 3-D resolution recovery, attenuation, and scatter correction algorithm. The CT component is typically performed with X-ray tube peak voltage of 130 kV, beam collimation of 2x1mm and nominal tube current–time product of 50 to 90 mAs, tuned by X-ray tube current modulation and Automatic Exposure Control (AEC). Images of the extremities must be reconstructed by B70 kernel with 1 to 1.25 mm slice thickness. CT soft tissue reconstruction (B20 kernel) may be necessary too, in order to analyze pedal entheses or soft tissue lesions. SPECT/CT images are still preceded by conventional dynamic planar images (optional) obtained over 1 min and blood pool images acquired over 4 min. Interpretation is irst conducted through MIP-oriented two-dimensional, axial and MPR, display browsing. Three dimensional display such as fused volume rendering techniques (VRT), either on PACS or hybrid camera dedicated workstations, proves a useful diagnostic adjunct in localizing and patterning foot SPECT/CT abnormalities.

Abstracts

Carefully delineated pattern and localization of uptake abnormality on SPECT/CT images have replaced the rough ill-located hot spot on planar views. Even if pain is involving one foot, systematic inspection of regional (contralateral foot) and general (remaining skeleton) structures must be performed mainly in order to gather clues as to the nature (mechanical or non-mechanical) of the foot condition. SPECT/CT generates sectional images with remarkably enhanced resolution, portraying the topographic landmarks and pathological alterations of miscellaneous foot and ankle conditions in great detail.

34

The interobserver agreement in analysis of SPECT/CT images is signiicantly higher compared with that of planar and (stand-alone) SPECT images 4–5. Bone SPECT/CT, as planar scintigraphy, has been valued for its sensitivity for radiographically occult stress (fatigue or insuiciency) fractures in the foot and ankle (X-rays sensitivity = 20%), symptomatic accessory ossicles, osteoid osteoma (afecting the foot in 10% of cases), cryptic osteomyelitis, calcaneonavicular coalition, rheumatic disease (rheumatoid arthritis, spondyloarthropathy, …)6 SPECT/CT has added value in localising active degenerative joint disease in the foot and ankle with multiple arthritic joints.

EANM 13


Bone hybrid imaging dramatically enhanced speciicity in a such level that nowadays some disorders hypothesized in SPECT/CT report were never or poorly conjectured on a bone planar scintigraphy report at the era of planar scintigraphy (eg distal tibioibular syndesmosis injuries, Lisfranc or tarsometatarsal joint complex injuries, osteochondral lesions of the talus, neuropathic osteoarthropathies, microcrystalline arthropathies, pedal enthesopathies,…)7. Moreover, integrative SPECT/CT interpretation allows to convey a diagnosis of rarer conditions (eg Muller-Weiss syndrome, synovial osteochondromatosis, pigmented villonodular synovitis, primitive bone tumours, acrometastases,…). References Paycha F, Ramadan A, Rezgui M, Aubert F, Levesque M. Conduite à tenir devant des douleurs du pied avec des radiographies normales: quelle place aujourd’hui pour la scintigraphie parmi les nouvelles techniques d’imagerie ? GETROA Opus XXIX, pp 425-468, Editions Sauramps médical, Montpellier, 2002

2.

Hosahalli KM, Gnanasegaran G, Vijayanathan S, Fogelman I. SPECT/CT in imaging foot and ankle pathology— The demise of other coregistration techniques. Semin Nucl Med 2010; 40:41-51

3.

Linke R, Kuwert T, Uder M, Forst R, Wuest W. Skeletal SPECT/CT of the peripheral extremities. AJR 2010; 194:W329–W335

4.

Pagenstert GI, Barg A, Leumann AG, Rasch H, Müller-Brand J, Hintermann B, Valderrabano V. SPECT-CT imaging in degenerative joint disease of the foot and ankle. J Bone Joint Surg [Br] 2009; 91-B: 1191-6

5.

Girma A, Ramadan A, Benisvy D, Malek Z, Fontana X, Darcourt J, Paycha F. Comparison of intrareader and inter-reader reproducibility in planar, SPECT and SPECT/CT bone scintigraphy in exploring a painful foot. Primacy of a standardised semiology [Article in French]. Méd Nucl 2010; 34: 513–527

6.

Nathan M, Mohan H, Vijayanathan S, Fogelman I, Gnanasegaran G. The role of 99mTc-diphosphonate bone SPECT/CT in the ankle and foot. Nucl Med Commun. 2012; 33 (8): 799-807

7.

Meftah M, Katchis SD, Scharf SC, Mintz DN, Klein DA, Weiner LS. SPECT/CT in the management of osteochondral lesions of the talus. Foot Ankle Int 2011; 32 (3): 233-8

Abstracts

1.

35


6d

ǚ The Referred Pain – When the Causative Lesion Lies Far from the Aching Joint W. van der Bruggen (Doetinchem) Imaging of a single joint will fail to explain the patients’ pain in many cases, especially in patients with referred pain. Nuclear medicine is traditionally known for imaging multiple joints or even the total body, being of potential extra value in patients with referred pain. The deinition and pathophysiology of referred pain and the diference with radicular pain will be discussed1,2. Pain in the thigh and pain in the knee can be the result of referred pain and it is therefore important for any nuclear medicine physician to choose the right imaging protocol in order to be able to recognize possible referred pain. The strengths and shortcomings of nuclear medicine techniques in referred pain in relation to the limping patient will be discussed3–6. This part of the CME also aims to hand a clear overview of the pathophysiology of referred pain in the thigh, in the knee and in lower limb pain originating from the spine. Low back pain is very closely related to the limping patient (with and without referred pain). Chronic low back pain is generally over treated 4. In daily practice it can be challenging to decide whether a patient with chronic low back pain will beneit from (imaging) diagnostics, or not. Furthermore, there is a wide variety of imaging techniques to choose from for each speciic patient, both radiological and nuclear medicine techniques. Unnecessary imaging of the low back may contribute to more unnecessary investigations and unnecessary treatment. In selected patients with chronic low back pain, however, scintigraphy can be very useful. For example one speciic strength of bone scintigraphy is predicting whether a patient with chronic low back pain will beneit from facet joint injections4. In selected limping patients imaging with bone scintigraphy with the right protocol of the low back may reveal the origin of referred pain in the thigh or knee. Cases of SPECT/CT scans in limping patients and of patients with low back pain will be presented to demonstrate the usefulness of this technique in selected limping patients (with or without low back pain). As stated above, deciding on the best imaging technique in limping patients (with or without low back pain) and choosing the right imaging protocol is challenging. Guidelines for when to use the bone scan (both planar and with SPECT/CT) or other nuclear medicine techniques can be very helpful in imaging the limping patient (with or without low back pain)3,6.

Abstracts

References 1.

Niv D, Kreitler S, Diego B, Lamberto A: Taxonomy and classiication of pain. The Handbook of Chronic Pain. Nova Biomedical Books; 2007

2.

Howe JF, Loeser JD, Calvin WH: Mechanosensitivity of dorsal root ganglia and chronically injured axons: a physiological basis for the radicular pain of nerve root compression. Pain 1977 Feb;3(1):25-41.

3.

ACP Issues Guidelines for Diagnostic Imaging for Low Back Pain, 2011.

4.

Deyo RA, Mirza SK, Turner JA, Martin BI: Overtreating chronic back pain: time to back of? J Am Board Fam Med. 2009 Jan-Feb;22(1):62-8.

5.

Low Back Pain: Prediction of Short-term Outcome of Facet Joint Injection with Bone Scintigraphy, by Spiros G. Pneumaticos, et al. Radiology 2006 Feb;238(2):693-8.

6.

Emilio Bombardieri, Cumali Aktolun, Richard P. Baum, Angelica Bishof-Delaloye, John Buscombe, Jean François Chatal, Lorenzo Maioli, Roy Moncayo, Luc Mortelmans, Sven N. Reske: Bone scintigraphy procedure guidelines for tumour imaging, European Journal of Nuclear Medicine and Molecular Imaging December 2003, Volume 30, Issue 12, pp B99-B106.

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CME VII: Paediatrics

Abstracts

Thyroid Diseases in Children

37


7a

ǚ Hypothyroidism and Hyperthyroidism in Children: Role of Nuclear Medicine B.O. Helal (Orsay) Thyroid imaging with isotopic iodine (123I) or 99mTc pertechnetate has been available for decades and is essentially used in newborn infants diagnosed with congenital hypothyroidism (CH). Hypothyroidism may be transient, especially after iodine overload or permanent due to thyroid dysgenesis (ectopia, hypoplasia and athyrosis) or to autosomal recessive dyshormonogenesis occurring in eutopic glands. Thyroid scintigraphy (TS) performed either with 99mTc pertechnetate or 123I permits a precise characterisation of the aetiology which is important for clinical management. However, recent reports have shown that 123I TS is the best procedure. It will identify ectopic thyroid tissue which is the commonest cause of CH and in cases of eutopic thyroid, the measurement of 123I uptake before and after perchlorate administration evaluates the iodine organiication process. Scintigraphy should be carried out early within 7 days of starting thyroxine treatment. In contrast, isotopic procedures for imaging of thyrotoxicosis which has a very low incidence in paediatric patients, are rarely necessary. Thyrotoxicosis may be transient especially in neonates, most often due to a transplacental passage of maternal thyroid-stimulating immunoglobulins rapidly resolving or permanent due in about 90 % of patients to Graves’ disease. TS could be performed if a nodule is palpable or when radioactive treatment is considered. 131I therapy of Graves’ disease was introduced more than 60 years ago and its use has been reported in more than 1200 children with remission rates exceeding 95 %. 131I iodine treatment could be considered for second or third-line therapy for children aged 10 years or older with anti-thyroid drug failure, severe complications or poor compliance. References Schoen EJ, Clapp W, To TT and Fireman BH. The key role of newborn thyroid scintigraphy with isotopic iodide (123I) in deining and managing congenital hypothyroidism. Pediatrics. 2004; 29: 683-688

2.

M de Vijlder JJ. Primary congenital hypothyroidism: defects in iodine pathways. Eur J Endocrinol. 2003; 149:247-256

3.

LaFranchi SH. Approach to the diagnosis and treatment of neonatal hypothyroidism. J clin Endocrinol Metab. 2011; 96:2959-67

4.

Williamson S, Greene SA. Incidence of thyrotoxicosis in childhood: a national population based study in UK and Ireland. Clinical Endocrinology. 2010; 72: 358-363

5.

Rivkees SA. Pediatric Graves’ disease: contreversies in management. Hormon Res Paediatr. 2010; 74:305-311

6.

Rivkees SA, Dinauer C. An optimal treatment for pediatric Graves’ disease is radioiodine. J Clin Endocrinol Metab. 2007; 92:797-800

Abstracts

1.

38

7b

ǚ Paediatric Thyroid Cancer R. Howman-Giles (Sydney) Diferentiated thyroid cancer (DTC) is rare in childhood however it is the most common endocrine malignancy in children. Childhood DTC more often presents with advanced disease compared to adults. This is particularly from loco-regional involvement but distant metastases also occur more frequently. Management is by surgical resection usually near or total thyroidectomy and with radioiodine therapy, which results in favourable outcomes. This review details current opinions of management of paediatric DTC.

EANM 13


The annual incidence of paediatric DTC is 0.54 per 100,000 patients and there is an annual increase in incidence of 1.1% per year. There is a signiicant diference in biological behaviour between paediatric patients and adults. Paediatric DTC more often has a larger tumour volume at presentation, more aggressive behaviour, with more frequent cervical lymph node (42–90%) and distant metastases (7–20%) and higher recurrence rate (65–90%), but longer overall survival (>95%). Extensive pre-surgical staging is not usually undertaken for thyroid carcinoma. Ultrasound is important at diagnosis, for biopsy and prior to surgery to determine nodal involvement. Other imaging in particular pulmonary CT maybe required. There are many post operative staging systems for DTC but most predict mortality rates rather than recurrence. Radioiodine whole body scintigraphy (WBS) after near or total thyroidectomy remains the most important staging procedure in DTC to detect residual thyroid tissue, loco-regional disease and distant metastases. Staging with 123I or 131I WBS allows: better prognostication for the patient i.e. risk of recurrence and mortality, ability to tailor management decisions regarding RAI therapy i.e. ablation or adjuvant therapy, decisions on TSH suppressive therapy and management decisions regarding follow up i.e. low or high risk. Near or total thyroidectomy is the primary therapy for DTC in paediatric patients due to the high incidence of loco-regional metastatic disease, distant metastases and higher recurrence rate. This also allows more accurate follow up using serum thyroglobulin (Tg) and 123I or 131I WBS. In children it is imperative that experienced thyroid surgeons perform the surgery, as there is good correlation with the rate of complications and this expertise. The goals of RAI in the primary treatment of DTC are to eradicate the disease and extend overall survival but importantly to extend recurrence free survival (RFS). Controversy arises in the use of RAI in that paediatric patients maybe more sensitive to side efects of RAI, including induction of second cancers. The dose schema for children and adolescents is now most commonly based on the adult dose adjusted by weight or body surface area. Long term follow is based on periodic physical examination, disease surveillance laboratory tests in particular assessment of serum Tg and Tg antibodies while on suppressive T4, and depending on the initial stage of the disease, a 123I or 131I WBS of T4 or after rTSH stimulation. At this time measurement of serum Tg and TSH is required. Ultrasound of the neck is indicated at this time particularly if there was loco-regional disease at presentation. If abnormal masses are detected then FNAB is indicated. Measurement of Tg in the aspirate can be performed. If there was evidence of pulmonary metastases or other distant metastatic disease appropriate imaging i.e. non-contrast pulmonary CT is undertaken. Serum Tg is the most sensitive indicator of tumour recurrence after near or near total thyroidectomy and remnant ablation. Serum Tg >2–3ug/L with rTSH stimulation or 8ug/L after T4 withdrawal is diagnostic of recurrence of DTC. In patients with elevated Tg but negative 123I or 131I scans, 18F-FDG PET/CT maybe of value.

Abstracts

Clinical presentation, initial diagnosis and staging, the use of RAI therapy, regimes for follow up in diferent stages of disease will be discussed.

39


References Rivkees SA, Mazzaferri EL, Verburg FE, Reiners C, Luster M, Breuer CK, Dinauer CA, and Udelsman R. The Treatment of Diferentiated Thyroid Cancer in Children: Emphasis on Surgical Approach and Radioactive Iodine Therapy. Endocrine Reviews 32:798–826, 2011

2.

Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, Brokhin M,Omry G,Fagin JA,Shaha A. Estimating Risk of Recurrence in Diferentiated thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation: Using Response to Therapy Variables to Modify the Initial Risk Estimates Predicted by the New American Thyroid Association Staging System.Thyroid 20(12):1341-1349, 2010

3.

Reiners C, Hanscheid H, Luster M, Lassmann M, Verburg FA. Radioiodine for remnant ablation and therapy of metastatic disease.Nat. Rev. Endocrinol. 7,589-595, 2011

4.

Verburg FA, Biko J, Diessl S, Demidchik Y, Drozd V, Rivkees SA, Reiners C, Hanscheid H. I131 Activities as High as Safely Administrable (AHASA) for the Treatment of Children and Adolescents with Advanced Diferentiated Thyroid Cancer. J Clin Endo Metabolism 96:E1268-E1271, 2011

5.

Pawelczak M, David R, Franklin B, Kessler M, Lam L, Shah B. Outcomes of Children and Adolescents with Well Diferentiated Thyroid Carcinoma and Pulmonary Metastases Following 131I Treatment: A Systematic Review. Thyroid 20:1095-1101, 2010

Abstracts

1.

40

7c

ǚ Dosimetry and Short/Long-Term Consequences of Radioiodine Treatment in Children and Teenagers F.A. Verburg (Aachen) Pediatric diferentiated thyroid cancer (DTC) patients not infrequently present with lymph node and/or distant (lung) metastases. Such patients warrant an aggressive treatment consisting of surgical removal of all surgically accessible metastases as well as further therapy with one or more courses of radioiodine therapy (RAI) [1].

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It is still subject of debate in literature how much I-131 should be given in pediatric patients during RAI. Patients can either be given a ixed (possible body weight adjusted) activity or a dosimetry based activity which is usually considerably higher. Multiple administrations of lower activities in a “fractionated” RAI lead to changes in tumor/lesion biokinetics. The dose to the target tissue per administered amount of activity declines with subsequent therapies, suggesting that the least radioiodine avid cells are more likely to remain unafected when a submaximal activity of I-131 is given [2]. This results in a loss of therapeutic eicacy along the sequence of ixed activity administrations. Therefore, the administration of a single, high I-131 activity is likely more efective than the administration of the same activity cumulatively spread over multiple RAI courses. Conditions during dosimetry should mimic those during therapy with regard to the iodine excretion rates: i.e. patients to be treated in hypothyroidism should be hypothyroid during dosimetry as well, whereas those treated with recombinant human TSH on a compassionate use basis are best examined during levothyroxine therapy. In general, two opposite approaches to dosimetry exist [3]: - either the activity that is as high as safely administrable (AHASA) is determined based on the radiation exposure to the critical organs at risk (in pediatric patients these are the bone marrow and, in patients with lung metastases, the lungs)[4], - or a lesion based approach in which the activity that is required to deliver a certain radiation dose to the lesion is determined. As the latter approach requires an accurate volumetry of the target lesion(s), which in children with disseminated pulmonary metastases which are usually not visible with morphologic imaging techniques, we advocate using the AHASA approach in children.

The extent of harmful efects of high cumulative I-131 activities is still debated. High activities may induce leukaemia. Furthermore, the risk of second primary tumours may be elevated after I-131 therapy, and a signiicant excess mortality due to non-thyroid malignancies in survivors of pediatric DTC was observed [5]. Others did not observe secondary malignancies during a median 11.3 years follow-up after the last RIT in a large pediatric cohort [1]. Other potential side efects of high activity RAI like permanent xerostomia can also severely impact quality of life. It is therefore important to select the right treatment for the right patients, and use the minimum amount of I-131 necessary to achieve the desired goal. Overtreatment with the risk of causing more harm than good should be avoided according the old principle of medicine “primum non nocere”.

41

Abstracts

Which patient will requires dosimetric RAI? In patients with uncomplicated cases of a radically resected DTC who only show low Tg levels without a clear remaining morphologic correlate in ultrasound, CT or MRI imaging, it is likely that a normal, ixed activity RAI will suice to achieve a disease-free status. Adjustment of the administered activity for bodyweight should be the minimum individualization in this setting. Dosimetry is typically reserved to selected patients with extensive cervical lymph node metastases or distant metastases. Lesion dosimetry can be an option when the disease is limited to cervical lymph node metastases where the masses can be determined accurately with X-ray computer tomography (CT) or magnetic resonance imaging (MRI). Re-operation must be considered as well in these patients.


References Reiners C, Biko J, Haenscheid H, Hebestreit H, Kirinjuk S, Baranowski O et al. Twenty-Five Years after Chernobyl: Outcome of Radioiodine Treatment in Children and Adolescents with VeryHigh-Risk Radiation-Induced Diferentiated Thyroid Carcinoma. J Clin Endocrinol Metab 2013.

2.

Samuel AM, Rajashekharrao B, Shah DH. Pulmonary metastases in children and adolescents with well-diferentiated thyroid cancer. J Nucl Med 1998;39:1531-1536.

3.

Lassmann M, Hanscheid H, Verburg FA, Luster M. The use of dosimetry in the treatment of differentiated thyroid cancer. Q J Nucl Med Mol Imaging 2011;55:107-115.

4.

Lassmann M, Haenscheid H, Chiesa C, Hindorf C, Flux G, Luster M. EANM dosimetry committee series on standard operational procedures for pre-therapeutic dosimetry I: blood and bone marrow dosimetry in diferentiated thyroid cancer therapy. Eur J Nucl Med Mol Imaging 2008;35:1405-1412.

5.

Hay ID, Gonzalez-Losada T, Reinalda MS, Honetschlager JA, Richards ML, Thompson GB. Longterm outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008. World J Surg 2010;34:1192-1202.

Abstracts

1.

42

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CME VIII: Inlammation & Infection

Abstracts

The Diabetic Patient

43


8a

ǚ Nuclear Medicine Procedures and Clinical Indications in Diabetic Patients with Infection (With Special Emphasis on FDG Imaging) O. Israel (Haifa) Diabetes Mellitus (DM) is considered to represent the new epidemic and can be associated with severe chronic complications such as retinopathy, nephropathy, cardiovascular diseases and neuropathy. Functional and metabolic imaging plays an important role in assessing various challenging clinical scenarios in patients with DM. Nuclear medicine tests are employed in the evaluation of diabetic complications such as coronary heart disease, left ventricular function and renal disorders (as discussed in present symposium). There is increasing evidence that F-18 luorodeoxyglucose (FDG) imaging is, in addition to cancer, also a good alternative for assessment of infection and inlammation. Hypermetabolic cells in malignant or infectious processes, are characterized by high glucose uptake and an increased rate of glycolysis. Glucose and FDG are transported across cell membranes by GLUT proteins, with a potentially increased competition in the presence of increased blood glucose levels. Nearly 50% of diabetics have had at least one hospitalization for infectious processes that can involve the foot, urinary tract, fungal disease, malignant otitis externa, cholecystitis, pyomyositis and necrotizing fasciitis. The impact of hyperglycemia and DM on FDG imaging has been evaluated. High glucose levels but not DM have been found to afect the detection rate of cancer by FDG imaging. However, neither DM nor hyperglycemia had an efect on the number of false negative FDG studies in patient with suspected infection. In addition to FDG, the main SPECT imaging agents for assessment of infection are leucocytes (WBCs) labeled with either Tc-99m or In-111. The diabetic foot is a severe clinical problem and a common cause for morbidity and mortality in patients with DM, with osteomyelitis occuring in up to 15% of cases. The principal current unmet clinical needs are to determine when bone infection is present and to more clearly deine when infection has resolved. Diferential diagnosis with soft tissue infection and Charcot joint is often diicult. SPECT/CT using labeled WBCs as well as FDG-PET/CT are imaging alternatives that should be considered. If either WBC-SPECT/CT or FDG-PET/CT indicates the presence of osteomyelitis or if the study is most compatible with soft tissue but not bone infection, treatment should be selected accordingly.

Abstracts

Vascular grafts replace or bypass occluded or diseased blood vessels in order to maintain the oxygen supply to their speciic territory. Graft infection following prosthetic vascular reconstruction is an uncommon but severe complication. Infection can be caused by, among others, patient-related factors such as DM that was found in one third of the patients with infected vascular grafts. Diagnosis of a prosthetic vascular graft infection can be diicult but is essential for the correct choice of treatment. False positive results may lead to unnecessary surgery while failure to diagnose graft infection may have life-threatening sequels. WBC imaging, lately with SPECT/CT, and FDG imaging can provide reliable, non-invasive diagnostic information. The precise anatomic localization of increased WBC or FDG uptake provided by the CT component of SPECT/CT or PET/CT enables accurate diferentiation between graft and adjacent soft tissue infection increasing the diagnostic accuracy with a subsequently optimized therapeutic strategy.

44

References Bar-Shalom, R., Yefremov N, Guralnik L, et al. SPECT/CT using 67Ga and 111In-labeled leukocyte scintigraphy for diagnosis of infection. J Nucl Med, 2006;47:587-594

2.

Rabkin Z, Israel O, Keidar Z. Do hyperglycemia and diabetes afect the incidence of false negative 18F-FDG-PET/CT studies in patients evaluated for infection or inlammation and cancer? A comparative analysis. J Nucl Med 2010;1015-1020

3.

Familiari D, Glaudemans AW, Vitale V, et al. Can sequential 18F-FDG PET/CT replace WBC imaging in the diabetic foot? J Nucl Med. 2011;52:1012-1019

4.

Antonios VS et al., Prosthetic vascular graft infection: a risk factor analysis using a case-control study. J Infect, 2006. 53(1): p. 49-55

5.

Keidar Z, Engel A, Hofman A, et al. Prosthetic vascular graft infection: the role of 18F-FDG PET/ CT. J Nucl Med 2007;48:1230–1236

Abstracts

1.

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45


8b

ǚ Diabetic Nephropathy and Imaging of Kidney Infections and Graft Rejection J. Buscombe (Cambridge) Diabetes remains the most common cause of renal failure within the developed world 1. The resulting requirement for renal replacement therapy puts a signiicant burden on both the individual with costs running into € 1,000 per patient per year and the possibility that up to 10% of the population sufering from diabetes by the mid 21st century this is clearly a major public health issue. The cause of renal failure in diabetics is complex and can involve both the poor control of the diabetes with a direct toxic efect on the kidney but also co-existent cardiovascular disease can result in hypertension further resulting in an increased chance of irreversible renal damage. The two options for treatment is renal replacement therapy (dialysis) or transplantation. However renal failure itself can cause hypertension which can result in cardiovascular damage so there is often a vicious cycle of events. In addition even renal replacement therapy can not replace all the functions of the normal kidney so that cholesterol is often high and triglycerides reduced. This can result in increasing atheroma. Therefore nuclear medicine techniques may be needed to image patients on dialysis to determine if they have signiicant myocardial ischaemia 2. Therefore many centres have initiated routine myocardial perfusion imaging (MPI) in diabetic patients on dialysis and “silent” ischaemia and infarcts are not unknown 3. For those who may be on a list for transplantation for many years this may need to be repeated on two or three yearly. As atheroma efects the peripheral vessels as well there may be peripheral damage for example leading to the diabetic foot the topic of Prof Isreal’s. A recently diagnosed problem is that during haemodialyis the blood pressure may drop and those with stif carotid arteries may have a drop in cerebral perfusion leading to infarcts especially along the borders of the cerebral artery territories – so called watershed infarcts 4. This can lead to signiicant cognitive impairment but can be imaged with regional cerebral perfusion agents. If the patient is fortunate they will be ofered a transplant. Present practice is to keep the native kidneys in situ and transplant the kidney onto the right or left iliac artery. Nuclear medicine techniques can be used to monitor the health of this transplant. In the acute phase there may be urinary leak, acute rejection, vascular damage or severe ATN, Renography, normally with Tc-99m MAG3 provided the best test by which these can be monitored. Perfusion of the kidney can be compared with the ipsilateral iliac artery and the resulting “Hilson” index may vary from patient to patient but changes to the Hilson index within a patient are signiicant 5. In the less acute stage problems may be rejection, lymphoceole or infection. Though anti relux surgery is normally performed the short ureter which has been denervated by surgery increases the possibility of pyleonephritis. Acute positive imaging of such an infection was often problematic and the infections was often mild, and many agents used to image infection such as Tc-99m HMPAO leucocytes or Tc-99m anti-granulocyte antibodies would be excreted via the kidney. However the recent advent of SPECT/CT has allowed accurate locaisation of uptake which can help identify the site of infection especially if combined with agents such as Ga-67 citrate or In-111 leukocytes.

Abstracts

As with children’s kidneys pyleonephritis can result in renal scars and as with children this is best documented with DMSA imaging. However the position of the kidney in the pelvis and attenuation of the overlying iliac bone can make imaging diicult so SPECT may be more useful. Therefore nuclear medicine techniques are important and remain so for the time that the patient is irst found to have diabetic nephropathy, through transplant and beyond. Good safe practice for these patients depends on high quality and consistent nuclear medicine.

46

References Hill CJ, Fogarty DG. Changing trends in end-stage renal disease due to diabetes in the United Kingdom. J Ren Care. 2012;38 Suppl 1:12-22

2.

Steenkamp R, Castledine C, Feest T. Chapter 6 Survival and causes of death of UK adult patients on renal replacement therapy in 2010: national and centre-speciic analyses. Nephron Clin Pract. 2012;120 Suppl 1:c105-35

3.

Caglar M, Mahmoudian B, Aytemir K, Kahraman S, Arici M, Kabakci G, Karabulut E. Value of 99mTcmethoxyisobutylisonitrile (99mTc-MIBI) gated SPECT for the detection of silent myocardial ischemia in hemodialysis patients: clinical variables associated with abnormal test results. Nucl Med Commun. 2006;27:61-9

4.

Davenport A, Buscombe JR Watershed cerebral infarction in a hemodialysis patient Kidney Int. 2010;77:114

5.

Hilson AJ, Maisey MN, Brown CB, Ogg CS, Bewick MS. Dynamic renal transplant imaging with Tc-99m DTPA (Sn) supplemented by a transplantperfusion index in the management of renal transplants. J Nucl Med. 1978;19:994-1000

6.

Navalkissoor S, Nowosinska E, Gnanasegaran G, Buscombe JR Single-photon emission computed tomography-computed tomography in imaging infection. Nucl Med Commun. 2013;34:283-9

7.

Dupont PJ, Psimenou E, Lord R, Buscombe JR, Hilson AJ, Sweny P. Late recurrent urinary tract infections may produce renal allograft scarring even in the absence of symptoms or vesicoureteric relux. Transplantation. 2007;84:351-5

Abstracts

1.

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47


8c

ǚ Imaging Cardiovascular Diseases in Diabetic Patients R. Slart (Groningen) Despite advances in medical therapy, cardiovascular disease (CVD) remains the leading cause of mortality among patients with diabetes mellitus (DM). The macrovascular complications of diabetes, CVD, cerebrovascular disease, and peripheral vascular disease, account for more than 70% of all deaths in individuals with diabetes. CVD events are four times more common in individuals with diabetes, occur at a younger age, and have a much greater case fatality rate. In fact, people with diabetes and no history of vascular disease have the same risk of having a heart attack or dying of vascular disease as nondiabetic individuals with a prior history of vascular disease. The occurrence of DM and CVD increases with age; both are associated with an adverse lipid proile, obesity, and a sedentary lifestyle. DM is related to the development of atherosclerosis & microvascular disease, the cardio-renal syndrome and cardiac autonomic diabetic neuropathy. Currently, the most widely used nuclear medicine technique to image myocardial functions are myocardial perfusion scintigrapy (MPS) and left ventricular function assessment (MUGA, gated MPS), using SPECT and PET techniques. Today, CT is commonly added to calculate coronary calcium scoring, and when available CT angiography for coronary stenosis assessment. Several SPECT MPS en PET MPS studies involving the stratiication of diabetic patients and are getting transparent in international guidelines. The new goal in nuclear medicine is to image cardiovascular disease directly linked to the underlying processes of diabetes, most importantly atherosclerosis activity. [18F]-FDG is playing an important role in this ield. Novel targeted imaging (molecular imaging) of diferent processes in atherosclerotic plaques using speciic radiopharmaceuticals are under development. Processes to be mentioned are inlammation, angiogenesis, apoptosis, and microcalciication. Further, cardiac autonomic diabetic neuropathy (CADN) is a common and serious complication of diabetes mellitus, which consists of damage to the autonomic nerve ibres that innervate the heart and blood vessels, resulting in alterations in heart rate control and vascular dynamics, associated with disabling clinical manifestations and increased mortality and incidence of both silent myocardial ischaemia and infarction. [123I]mIBG SPECT and [11C]mHED PET are used for the evaluation of the pre-synaptic nerve activity, whereas [11C]-CGP12388 PET is used for the quantiication of the post-synaptic nerve activity (beta-adrenoceptor).

Abstracts

This educational lecture presents an overview of cardiovascular imaging in diabetic patients by a variety of (novel) nuclear medicine techniques and radiopharmaceuticals, in the era of diagnosis, prognosis, evaluation and projected against the current guidelines.

48

References 1.

Grundy SM, Benjamin IJ, Burke GL, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals From the American Heart Association. Circulation. 1999;100:1134-1146

2.

Rajagopalan N, Miller TD, Hodge DO, et al. Identifying high-risk asymptomatic diabetic patients who are candidates for screening stress single-photon emission computed tomography imaging. J Am Coll Cardiol. 2005;45:43-49

3.

Rydén L, Standl E, Bartnik M, and other task force members. Guidelines on diabetes pre-diabetes, and cardiovascular diseases: executive summary. TheTask Force on diabetes and Cardiovascular diseases of the European Society (ESC) and of the European Association for the Study of diabetes (EASD). Eur Heart J. 2007 Jan;28(1):88-136

4.

Glaudemans AW, Slart RH, Bozzao A, et al. Molecular imaging in atherosclerosis. Eur J Nucl Med Mol Imaging. 2010 Dec;37(12):2381-97

5.

Masteling MG, Zeebregts CJ, Tio RA, et al. High-resolution imaging of human atherosclerotic carotid plaques with micro 18F-FDG PET scanning exploring plaque vulnerability. J Nucl Cardiol. 2011 Dec;18(6):1066-75

6.

Holm PW, Slart RH, Zeebregts CJ, et al. Atherosclerotic plaque development and instability: a dual role for VEGF. Ann Med. 2009;41(4):257-64

7.

Slart RH, Zeebregts CJ, Hillege HL, et al. Myocardial perfusion reserve after a PET-driven revascularization procedure: a strong prognostic factor. J Nucl Med. 2011 Jun;52(6):873-9

8.

Murthy VL, Naya M, Foster CR et al. Association between coronary vascular dysfunction and cardiac mortality in patients with and without diabetes mellitus. Circulation. 2012 Oct 9;126(15):1858-68

9.

Flotats A, Carrió I. The role of nuclear medicine technique in evaluating electrophysiology in diabetic hearts especially with 123I-MIBG cardiac SPECT imaging. Minerva Endocrinol. 2009 Sep;34(3):263-71. Review

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10. Scholte AJ, Schuijf JD, Delgado V, et al. Cardiac autonomic neuropathy in patients with diabetes and no symptoms of coronary artery disease: comparison of 123I-metaiodobenzylguanidine myocardial scintigraphy and heart rate variability. Eur J Nucl Med Mol Imaging. 2010 Aug;37(9):1698-705 11. Akabani G, Kennel SJ, Zalutsky MR. Microdosimetric Analysis of Particle–Emitting Targeted Radiotherapeutics Using Histological Images J Nucl Med 2003; 44:792–805. 12. AnderssonH, Cederkrantz E, Back T, Divgi C, Elgqvist J, Himmelman J. Intraperitoneal a-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of 211At-MX35 F(ab9)2—A Phase I Study J Nucl Med 2009; 50:1153–1160.

Abstracts

13. Hindorf C, Chittenden S, Aksnes A-K, Parker C, Flux GD Quantitative imaging of 223Ra-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases Nuc Med Comm (in press).

49


CME IX : Neuroimaging (Interactive) Brain PET Imaging Chairs:

J. Darcourt (Nice) P. Payoux (Toulouse)

Speakers:

F.M. Nobili (Genova): FDG-PET in the Context of the other Biomarkers in Prodromal AD P. Payoux (Toulouse): How to Read Amyloid Images? J. Darcourt (Nice): DOPA PET Neuroimaging

Abstracts

S. Hesse (Leipzig): PET-MRI Brain Imaging

50

EANM 13


CME X: ESNM Faculty (Interactive) PET/CT in Cancers of Unknown Origin or Paraneoplastic Syndromes Chairs:

C.A. Hoefnagel (Amsterdam) J.-N. Talbot (Paris)

Speakers:

S. Balogova (Bratislava): Cancer of Unknown Origin (CUP) F. Montravers (Paris): Neuroendocrine Cancer of Unknown Origin (CUPNET)

Abstracts

J.-N. Talbot (Paris): Paraneoplastic Syndromes

51


CME XI: ESNM Faculty (Interactive) Pitfalls in Nuclear Medicine Chairs:

L. Mansi (Naples) A.J. Britten (London)

Speakers:

D. Donner (Treviso), S. Agostini (Trento): How to Avoid Pitfalls “Before the Scan” A. J. Britten (London): Technical Pitfalls and Solutions

Abstracts

J. Buscombe (Cambridge): Unusual Clinical Pitfalls

52

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CME XII: Oncology

Abstracts

Cross-Sectional Imaging in Nuclear Medicine

53


12a

ǚ CT and MR in Musculoskeletal Pathologies: What the Nuclear Physician Should Know G. Tognini (La Spezia) Owing to the great number of tumors and tumor-like lesions of bone, accurate diagnosis of the nature of the process on the basis of its plain X-ray, CT and MR patterns is often not possible. Nevertheless, although the X-ray, CT and MR indings may not allow a simple diagnosis, they do provide reliable information regarding its aggressiveness or rate of growth, and this information, coupled with clinical data, allows the formulation of a reasonable diagnosis in most cases. Morphologic features that aid in the diferential diagnosis include the pattern of bone destruction, size, shape and margin of lesions, the presence of periosteal response, the pattern of cortical erosion and the presence of a soft tissue mass. Distribution of lesions within a bone provides additional important clues to the correct diagnosis. This lecture will address the CT and MR indings in musculoskeletal neoplasms, in order to provide to the nuclear medicine physician an overview of cross-sectional imaging features useful in their daily practice. References Leung JC, Dalinka MK. Magnetic Resonance imaging in primary bone tumors. Semin Roentgenol 2000; 35: 297-305

2.

Nomikos GC, Murphey MD, Kransdorf MJ, et al. Primary bone tumors of the lower extremities. Radiol Clin North Am 2002; 40: 971-990

3.

Miller SL, Hofer FA. Malignant and benign bone tumors. Radiol Clin North Am 2001; 39: 673-699

4.

Steinborn MM, Heuck AF, Tiling R, et al. Whole-body bone marrow MRI in patients with metastatic disease to the skeletal system. J Comput Assist Tomogr 1999; 23: 123-129

5.

Vogler JB, Murphy WA. Bone marrow imaging. Radiology 1988; 168: 679-693

Abstracts

1.

54

12b

ǚ SPECT/CT in Benign Bone Diseases G. Mariani (Pisa) The strength of radionuclide bone imaging lies in the underlying pathophysiologic mechanism(s) of 99mTc-diphosphonate uptake, linked to enhanced osteoblastic activity. Its clinical utility, sensitivity and speciicity was originally established based on planar imaging. The introduction of SPECT, then of hybrid SPECT/CT has further enhanced the role of radionuclide imaging in the differentiation between benign and malignant lesions of the bone. However, 99mTc-diphosphonate scintigraphy is very sensitive but nonspeciic. In fact, this imaging procedure afords visualization of the entire skeleton with an extremely high sensitivity (close to 100%), at least for metastatic lesions from breast and prostate cancer. However, its rather low speciicity often requires further investigation with, e.g., X-ray-based imaging, CT or MR. Besides accurate deinition of the lesion boundaries for primitive bone tumours, SPECT/CT ofers the unique opportunity to correlate the scintigraphic indings with anatomical images for better classiication of indeterminate, non-diagnostic bone lesions detected at 99mTc-diphosphonate scintigraphy in patients with extra-skeletal cancers. Thus, a protocol for complete bone evaluation should include threephase bone imaging (if the clinical indings point to a speciic location), delayed whole-body and spot images, complemented by SPECT over the region of interest or abnormality pinpointed on planar imaging.

EANM 13


The evidence in support of SPECT/CT is rapidly amounting but still relatively limited. To date, studies have suggested improved diagnostic conidence and speciicity in the diagnosis of various types of bone pathology. Therefore, SPECT can be considered as complementary to planar bone images helping to classify suspicious lesions as benign or malignant. Particularly in the spine, SPECT is more sensitive in detecting and localizing vertebral lesions than planar imaging, with 20%–50% increase in lesion detection. Vertebral indings on planar and SPECT imaging tend to follow predictable patterns that are likely to represent benign changes, often degenerative, and allow interpretation as no deinite evidence for metastatic bone disease. For example, bone lesions that extend outward beyond the extrapolated margin of the vertebra or show “bridging” of activity across the posterior arches or vertebral bodies of more than one vertebra can be attributed to a benign process. Many patients without a known oncologic condition experience unexplained pain in the extremities or in the back. Bone scan should be part of the algorithm for evaluating acute and chronic pain syndromes and is useful in identifying the location and the extent of the lesion. Potential indications for SPECT/CT in benign bone lesions include a very wide spectrum of diseases including rheumatologic conditions (such as, heterotopic ossiication and, among others, dermatomyositis and polymyositis), pain after orthopedic prosthesis, osteomyelitis, relex sympathetic dystrophy, metabolic bone disease (such as hyperparathyroidism or osteoporosis, with high risk for osteoporotic insuiciency fractures), Paget disease, trauma/fractures (such as pelvic, sacrococcygeal, and scaphoid fractures, often diicult to diagnose on plain X-ray and even on CT), sport injuries (stress fractures, microfractures and periosteal trauma). Spondylolysis, stressrelated microfractures induced by trauma too subtle to be detected on X-ray, can better be identiied with SPECT, which often demonstrates lesions not detected on planar bone scintigraphy. Overall, bone SPECT may detect lesions not identiied with X-ray-based imaging in 25%–40% of patients.

Abstracts

Among benign bone neoplasms, osteoid osteoma has a characteristic pattern of focal hyperemia on blood pool images and intense tracer localization in the “nidus” on delayed images. Histiocytosis may often present as polyostotic disease, and whole-body planar images, followed by SPECT of the area of interest, is useful to evaluate extent of disease.

55


Bone-seeking agents may accumulate also in soft-tissue tumors, pleural efusions, ascites, liver, or stroke. Proposed mechanisms of uptake include local tissue necrosis; damage causing increased tissue calcium deposition; hyperemia; altered capillary permeability; adsorption onto soft tissue calcium; and binding to enzyme receptors or denatured proteins. Since bone scintigraphy was introduced into the clinical practice long before the development of hybrid imaging, most of the typical patterns of bone scintigraphy have been deined based on functional imaging only. For example, hypertrophic pulmonary osteoarthropathy can readily be detected on planar whole body and spot images, similarly as avascular necrosis of the femoral head. In these cases, although SPECT imaging ofers important complementary information, planar images are systematically acquired and typically demonstrate the characteristic indings of all phases of avascular necrosis and bone infarcts.

Abstracts

On the other hand, when considering the direct combination of CT (SPECT/CT) to bone scintigraphy, it is important to note that the clinical usefulness and efectiveness of bone imaging was proven without CT. In some cases, radionuclide bone imaging without coregistered CT yields suicient information for diagnosis. Thus, before adding CT, we need to determine, in each case, if the CT will improve upon sensitivity, speciicity and diagnostic accuracy of radionuclide bone imaging alone. If so, then CT acquisition over a limited area (decreasing Dose Length Product and absorbed dose) should be performed.

56

12c

ǚ CT and MRI in Abdominal Cancers: What the Nuclear Physician Should Know P. J. Valette (Lyon) The imaging assessment of abdominal cancers is usually facing three types of question:

EANM 13


1) detection and characterization of primary tumors and metastases, 2) accurate determination of the local spread and metastatic extension of the disease with a speciic attention to the liver in terms of surgical resectability, 3) standardized evaluation of the response to cytotoxic or targeted chemotherapy. CT and MRI have been from long used to answer to each of these questions. Both techniques require relevant imaging protocols. The intravenous contrast injection, respectively iodine and gadolinium, is almost always needed to improve tumors detection. With multiple-phase volume acquisitions (arterial, venous and late), the enhancement may also help to characterize hypervascular, necrotic or ibrotic tumors when showing a speciic pattern of contrast uptake. If needed, water-CT enteroclysis or colonography can be performed for the imaging of bowel cancers. MRI also provides further informations by the combination of various methods of image acquisition. T2 sequences may evidence tumor necrosis, and also provide often a better detection of hepatocellular carcinomas or liver endocrine metastases. In/out of phase T1 sequences may demonstrate the fat content of a tumor. Fat suppression is useful for a better delineation of pancreatic, mesenteric or pelvic masses. With 3D MR-cholangiography, the biliary tree and the pancreatic duct may be visualized as they are with direct opaciication, allowing a clear picture of stenosis or obstruction due to an adjacent tumor. In addition to this morphological approach, cross-sectional imaging is now able to provide functional information. Difusion-weighted MRI shows a restriction of the water difusion signal related to the tumor hypercellularity. This signal combined to the image of a possible tumor mass on the anatomical view is now currently used to detect small or hidden tumors similarly to the picture of increased consumption of glucose into cancers with PET-FDG. In another ield, CT or MR perfusion are proposed for tumor response evaluation because they provide both anatomic and functional or metabolic change information during the treatment. Since the therapeutic eicacy of anti-angiogenics is based on the reduction in the extent and permeability of the tumor microcirculation, CT perfusion is from now a promising method for predicting the patient outcome before the end of treatment.

Abstracts

CT and MRI have relative advantages and drawbacks. CT is still playing an important role in oncology, speciically in the ield of the treatment monitoring, by showing images of high spatial resolution, with an almost perfect reproducibility, and easy to read for clinicians,. On the other hand, abdominal MRI ofers a better contrast resolution, has the advantage to often facilitate the characterization of tumors by using the variety of available sequences, while it may be hampered by respiratory or bowel movements artifacts. Both techniques have also limitations in some circumstances. Peritoneal carcinomatosis remains diicult to assess when limited to small lesions, and post-surgical or post-radiation scarring is often diicult to distinguish from active tumor. Therefore, the combination of all techniques, including FDG-PET, should be considered in all the cases with uncertain inal diagnosis after cross-sectional imaging. There is evidence from this point of view that PET/CT, when performed for an abdominal cancer, should be performed with optimal CT protocols including contrast injection, and that nuclear physicians should become experts in reading CT and MRI pictures.

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12d

ǚ PET-CT in Abdominal Cancers C. Tychyj-Pinel (Lyon) Positron emission tomography/computer tomography (PET/CT) is becoming increasingly important in oncology imaging. This technique is inding application in diagnosis, therapy planning, treatment response assessment and follow-up of oncological diseases. Combination of PET and CT provides an exact anatomical correlation for metabolic indings and improves not only the sensitivity, but mainly the speciicity with a better characterization of abnormal tracer uptake. PET/CT has become the standard positron imaging procedure, replacing standalone PET, with better crystals and faster electronics. Most recent PET/CT devices are equipped with multi-slices spiral CT and full diagnostic CT can now be combined with PET in a one-stop diagnostic imaging procedure using optimized acquisition protocols. Furthermore, in M staging, the whole body staging ability gives PET/CT advantage over other imaging modalities. The most commonly used tracer at present is the glucose analogue (FDG). FDG accumulation in tissue is proportional to the amount of glucose utilization. Increased metabolism of glucose is a characteristic of most cancers and is in part related to over-expression of glucose transporters and increased hexokinase activity. But certain histological types of cancers are less or non FDG avid. This is the case of mucinous adenocarcinoma, some low-grade lymphomas, malt lymphoma, well diferentiated neuroendocrine tumors and well-diferentiated hepatocellular carcinomas. FDG-PET/CT has a proven role in the staging and detection of colorectal cancer recurrence, in the management of gastrointestinal stromal tumors and aggressive lymphomas. Its role has shown promising in the assessment of treatment response in colorectal cancers. FGD PET/CT could also provide additional information useful in target volume delineation for radiation planning of anal cancer. Limitations to the use of FDG-PET/CT for evaluation of the gastro-intestinal tract and abdominal organs include the signiicant overlap between normal physiologic uptake and disease. These include bowel uptake due to physiologic, iatrogenic (i.e. metformine), and infectious and inlammatory processes. An understanding of the physiologic processes that account for non-malignant uptake allows one to better interpret PET/CT oncology studies. The key to being able to diferentiate malignant disease from “false-positive” uptake within the bowel often lies in scintigraphic pattern recognition and the ability to triangulate FDG uptake to normal – or abnormal structure detectable on CT images. Beyond metabolic pattern recognition, knowledge of CT features from pathologic or benign conditions can be essential in identifying incidental premalignant or malignant lesions, and infectious and inlammatory diseases. On the other hand, CT images of the post-surgical abdomen are sometimes diicult to interpret. Scarring or necrosis following chemo or radiation treatment is frequently indistinguishable from tumor by CT. In these cases, FDG PET can be very useful to precise equivocal CT results. Moreover, PET can bring a greater level of exhaustivity in CT reading, in particular in some anatomical regions often missed or complex like in peritoneal carcinomatosis diagnosis.

Abstracts

In abdominal oncology cross-sectional imaging, Positron emission tomography (PET) and computerized tomography (CT) are both state-of-the-art tools that allow physicians provide better diagnoses (fewer equivocal PET and CT readings) and therefore improve patient care.

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EANM 13


CME XIII: Translational Molecular Imaging: Joint EANM/ ESMI Session

Abstracts

Optical and Nuclear Imaging

59


13a

ǚ Nuclear and Fluorescent Tracers for Intraoperative Application R. G. Pleijhuis (Groningen) Combining innovative molecular biology and chemistry, scientists in the ield of cancer research have developed molecular imaging modalities for visualization of a wide variety of cellular and molecular processes. Most experience in translating this approach into the clinic has taken place with PET and SPECT. In addition, luorescence imaging has recently entered the clinical testing phase. Vibrant developments have been made in both imaging systems and tumor-targeted probes that are potentially suitable for human use. Of particular interest for clinical translation is near-infrared luorescence (NIRF), in which an external light source of a certain wavelength is used to excite a target luorescent molecule. Upon excitation, the luorescent molecule emits a photon of lower energy at a higher wavelength, which can subsequently be detected using a highly-sensitive camera system. Intraoperative NIRF imaging ofers a promising technique for real-time luorescence-guided surgery that is safe, simple to operate, fast, relatively inexpensive, has high resolution, and makes use of non-ionizing radiation. However, compared with PET, optical imaging does not provide non-invasive wholebody imaging, and the penetration depth of the signal is limited. Many of the current eforts in tumor imaging have focused on the development of tumor-targeted luorescent tracers, which are targeted towards certain biomarkers involved in cancer, such as growth signaling receptors, angiogenesis growth factors, tumor cell markers, and enzymes. To date, only a limited amount of luorescent tracers is available for clinical use, with indocyanine green being the only clinical grade luorescent tracer that emits photons in the near-infrared spectral range. In the short term, a second near-infrared luorophore (IRDye® 800CW from Li-COR Biosciences, Lincoln, USA) is expected to gain clinical approval. NIRF imaging can be used to visualize vital anatomical structures such as bile ducts, lymph vessels, and ureters during surgery in real-time. Several studies reported on the feasibility of non-invasive sentinel lymph node detection following subcutaneous injection of the non-speciic luorophore indocyanine green. Moreover, tumor-targeted luorescent probes have been applied in several animal studies to diferentiate malignancy from surrounding tissue, enabling luorescence-guided resection of the primary tumor and lymph node metastasis. Recently, the irst-in-human use of intraoperative tumor-speciic NIRF imaging was reported, showing the feasibility of real-time surgical visualization of tumor tissue in patients. In addition to optical imaging, nuclear tracers have great potential for intraoperative applications. With tumor-targeted antibodies bound to a radioactive label, tumor-speciic SPECT or PET is feasible in the clinical setting. The combination of optical and nuclear imaging modalities (i.e., multimodality imaging) can yield complementary information and ofer synergistic advantages over each modality alone.

Abstracts

Although challenges will continue to arise, molecular imaging has the potential to be a powerful and practical tool for a wide array of applications in cancer research and treatment, including non-invasive detection of early-stage cancer, image-guided biopsies and surgical procedures, and therapeutic monitoring of cancer.

60

References Van Dam GM, Themelis G, Crane LM, Harlaar NJ, Pleijhuis RG, Kelder W, et al. Intraoperative tumorspeciic luorescence imaging in ovarian cancer by folate receptor-α targeting: irst in-human results. Nat Med. 2011;17(10):1315-9

2.

Gaykema SB, Brouwers AH, Lub-de Hooge MN, Pleijhuis RG, Timmer-Bosscha H, Pot L, et al. 89ZrBevacizumab PET Imaging in Primary Breast Cancer. J Nucl Med. 2013; PMID: 23651946

3.

Luker GD, Luker KE. Optical imaging: current applications and future directions. J Nucl Med. 2008;49(1):1-4

4.

Mieog JS, Vahrmeijer AL, Hutteman M, van der Vorst JR, Drijfhout van Hoof M, Dijkstra J, et al. Novel intraoperative near-infrared luorescence camera system for optical image-guided cancer surgery. Mol Imaging. 2010;9(4):223-31

5.

Sevick-Muraca EM. Translation of near-infrared luorescence imaging technologies: emerging clinical applications. Annu Rev Med. 2012;63:217-31

6.

Sevick-Muraca EM, Sharma R, Rasmussen JC, Marshall MV, Wendt JA, Pham HQ, et al. Imaging of lymph low in breast cancer patients after microdose administration of a near-infrared luorophore: feasibility study. Radiology. 2008;246(3):734-41

7.

Tafreshi NK, Enkemann SA, Bui MM, Lloyd MC, Abrahams D, Huynh AS, et al. A mammaglobin-A targeting agent for noninvasive detection of breast cancer metastasis in lymph nodes. Cancer Res. 2011;71(3):1050-9

8.

Terwisscha van Scheltinga AG, van Dam GM, Nagengast WB, Ntziachristos V, Hollema H, Herek JL, et al. Intraoperative near-infrared luorescence tumor imaging with vascular endothelial growth factor and human epidermal growth factor receptor 2 targeting antibodies. J Nucl Med. 2011; 52(11):1778-85

Abstracts

1.

EANM 13


61


13b

ǚ PET and Optical Tomography in Small Animals F. Ducongé (Orsay) Positron Emission Tomography (PET) has been fused with diferent imaging modalities; mostly X-ray computed tomography (CT) and more recently magnetic resonance imaging (MRI). Since few years, the fusion of PET with optical imaging has been proposed. In contrast to PET imaging, the major problem in optical imaging is that light photons are strongly absorbed in the visible wavelength range and they are subject to high amount of scattering when travelling through tissue. To address this issue, luorescent difuse optical tomographic (fDOT) technique, also known as luorescence molecular tomography (FMT), has been developed since the 90s by several groups. This technology employs instruments that operate in a trans-illumination excitation mode, and use sophisticated reconstruction algorithms for reconstructing a 3D luorescence signal with similar resolution as PET. Although, fDOT is still only able to perform imaging inside tissue a few cm in depth, it is perfectly adapted to in vivo imaging in mice. Currently, several groups are working to develop instruments that could perform simultaneously both imaging modalities. Furthermore, several experiments have already been done to perform sequential fDOT/PET imaging acquisition before co-registration. Such approaches could be promising for cross-validation of imaging methods in both modalities or to provide synergic information monitoring several molecular pathways inside the same subject. Here, we propose to present some results that evaluate the additional beneits of fDOT/PET imaging1–3. References Garofalakis A, Dubois A, Kuhnast B, Dupont DM, Janssens I, Mackiewicz N, Dollé F, Tavitian B, Ducongé F (2010) In vivo validation of free-space luorescence tomography using nuclear imaging. Opt Lett 35(18):3024–3026

2.

Nahrendorf M, Keliher E, Marinelli B, Waterman P, Feruglio PF, Fexon L, Pivovarov M, Swirski FK, Pittet MJ, Vinegoni C et al (2010) Hybrid PET-optical imaging using targeted probes. Proc Natl Acad Sci U S A 107(17):7910–7915

3.

Garofalakis, A., Dubois, A., Theze, B., Czarny, B., Tavitian, B. and Duconge, F. (2012) Fusion of [(18) F]FDG PET with Fluorescence Difuse Optical Tomography to Improve Validation of Probes and Tumor Imaging. Mol Imaging Biol. [Epub ahead of print]

Abstracts

1.

62

13c

ǚ Cerenkov Luminescence Imaging S. Maitrejean (Paris) Cerenkov efect was discovered in the early year of the twentieth century but was only understood during the thirties and it became famous with the emergence of the nuclear industry as the blue light of the nuclear plant. It was then showed that the Cerenkov efect is actually a light shockwave which occurs when charged particles exceed the speed of light in a medium. Its theory is rather complex but well-known formulas allow to calculate the spectrum and the yield of the emitted light. In this educational session we will describe briely these formulas for a better understanding of what can be expect from Cerenkov efect.

EANM 13


Cerenkov efect was irst a curiosity and began to be used in the sixties for several purpose in physics (speed measurement of high energy particles). In health science since more than thirty years Cerenkov efect has been a traditional tools in molecular biology for in vitro measurement of typical high energy radioprobes as 32P. Nevertheless, due to its weakness, this phenomenon was only used for imaging purpose when transparent medium (water) were involved. We’ll do here a short review of conventional application of Cerenkov efect. The advent of optical molecular imaging and the dramatic improvement in the sensitivity of camera developed for bioluminescence imaging, have changed the situation. It has made possible the use of Cerenkov efect as an imaging method (so called CLI for Cerenkov Luminescence Imaging), as an alternate to PET imaging in the pre-clinical realm. Numerous papers describing the use of Cerenkov efect for measuring 18F and other common PET tracers has been published since four years1, 2. These papers put the emphasis on the high throughput of optical technics when compared to conventional TEP camera. Furthermore, in the preclinical domain, DOT (Diffuse optical tomography) algorithms allows to provide fast 3D information certainly not at the level of accuracy of conventional PET technics but nevertheless usable. In this lecture, we will have an overview of the hardware and software technics used for quantitative CLI. Theoretically, CLI request only Beta or electrons whose energy is higher than 300 KeV, but practically 500–600 Kev are required to get a reasonable light yield for typical injected doses. This condition is fulilled by a large number of isotopes and more than half of the elements of the periodic table exhibit isotopes illing this condition. It means that, potentially, CLI is today the most versatile method among the in vivo imaging technics based on radioprobes (SPECT, TEP). Particularly, certain isotopes dedicated to in vitro analysis, as 32P, or radioisotopes for beta-therapy like 131I and 90Y can be easily used as in vivo tracers with CLI. Interesting results have been published showing in vivo images of such tracers3. Even though the physics of light propagation in tissues make its use is more obvious in the preclinical domain, it seems today that CLI can have application in the clinic. Several groups around the world are working on its use for per-operatory imaging or in endoscopy4 whereas other are working on its use for portal imaging5. For these clinical applications, the hardware and software technics developed for pre-clinical CLI (3D, real time imaging) are extensively used.

Abstracts

As a conclusion to this lecture, CLI appears to be a promising method for both pre-clinical and clinical studies. It can’t replace PET imaging for all purpose but can be useful for high throughput screening or when the use of conventional PET camera is complex. Furthermore, it can also be used for isotopes that were impossible to image in vivo before, opening new ields of research.

63


References Boschi, F., Calderan, L., D’Ambrosio, D., Marengo, M., Fenzi, A.,Calandrino, R., Sbarbati, A., Spinelli, A.E., 2011. In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation. Eur. J.Nucl. Med. Mol. Imaging 38 (1), 120-127

2.

Roberstson, R., Germanos, M., Manfredi, M., Smith, P., Silva, M., 2011. Multimodal imaging with 18F-FDG Pet and Cerenkov luminescence imaging after MLN4924 treatment in a human lymphoma xenograft model.J. Nucl. Med. 52 (11), 1764-1769

3.

Klose, A., Tekabe, Y., Johnson, L. 2012. Multispectral Cerenkov light tomography with the SPN equations. J Nucl Med 2012; 53: 2405

4.

Hongguang Liu, Colin M. Carpenter, Han Jiang, Guillem Pratx, Conroy Sun, Michael P. Buchin, Sanjiv S. Gambhir, Lei Xing, and Zhen Cheng. 2012. Intraoperative Imaging of Tumors Using Cerenkov Luminescence Endoscopy: A Feasibility Experimental Study. J Nucl Med 2013, 53: 1-3

5.

Rongxiao Zhang, Adam K. Glaser, Scott C. Davis, David J. Gladstone and Brian W. Pogue. 2012. Time-gated Cherenkov emission spectroscopy from linear accelerator irradiation of tissue phantoms. Biomedical Optics and 3D imaging. OSA 2012

Abstracts

1.

64

Radionuclide Metabolic Therapy The brand new Technologist’s Guide – out now!

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