of the thigh mass demonstrated a malignant peripheral nerve sheath tumor (spindle cell) in association with neurofibroma consistent with a neurofibrosarcoma.
about half of the hyperplastic glands were still visible on the planar view 1 hr after tracer injection compared to more than 80% of adenomas. CONCLUSION
SPECT increases the sensitivity and specificity of parathy roid scintigraphy. It appears particularly useful for the location of mediastinal glands. Our method, which combines the advan tages of 99mTc-MIBI, FADS and SPECT, allows increased scintigraphic accuracy. REFERENCES 1. Potts JT. Ackerman IP. Barker CF. et al. Diagnosis and management of asymptomatic primary hyperparathyroidism: consensus development conference statement. Ann Intern Med 1991;! 14:593-597. 2. Norton JA Controversies, advances in primary hyperparathyroidism. Ann Surg 1992:215:297-299. 3. Beazley RM, Costa J, Ketcham AS. Reoperative parathyroid surgery. Am J Surg 1975:130:427-429. 4. Brennan MF, Marx SJ, Doppman J, et al. Results of reoperation for persistent and recurrent hyperparathyroidism. Ann Surg 1981:194:671-676. 5. Granberg P-O. Johansson G, Lindval! N, et al. Reoperation for primary hyperparathy roidism. Am J Surg 1982:143:296-300. 6. Wang CA Parathyroid re-exploration. A clinical and pathological study of 112 cases. Ann Surg 1977;186,n°2:140-145. 7. Prinz RA. Gamvros OI. Allison DJ. Flechter DR. Lynn AL. Reoperations for hyperparathyroidism. Surg Gynecol Obslet 1981:152:760-764. 8. Katz AD. Hopp D Parathyroidectomy. Review of 338 consecutive cases for histology, location and reoperation. Am J Surg 1982:144:411-415. 9. Palmer JA, Rosen IB. Reoperative surgery of hyperparathyroidism. Am J Surg 1982:144:406-410. 10. Anger HO. Tomography and other depth discrimination techniques. In: HiñeGJ, Sorenson JA, eds. Instrumentation in nuclear medicine, vol. 2. New York. NY: Academic Press; 1974:61-100. 11. Mathieu L, Budinger TF. Pinhole digital tomography. In: Proceedings of the First World Congress of Nuclear Medicine. Tokyo, Japan: 1974:1264-1266.
12. Vogel RA. Kirch D, Lefree M, et al. A new method of multiplanar emission tomography using a seven pinhole collimator and an Anger scintillation camera. J NucÃMed 1978:19:648-654. 13. Jarritt PH, Ell PJ, Myers MJ, et al. A new transverse section brain imager for single gamma emitters. J NucÃ-Med 1979:20:319-328. 14. Jarritt PH, Ell PJ. A new emission tomographic body scanner. NucÃ-Med Commun 1980:1:94-101. 15. Budinger TF. Physical attributes of single-photon tomography. J NucÃ-Med 1980:21: 579-592. 16. Cullum ID. Jarritt PH, Ell PH. Performance parameters, minimal detectable lesions and partial volume effects for two emission tomographic body units. NucÃ-Med Commun 1980:1:153. 17. Jaszczak RJ. Chang LT. Murphy PH. SPECT using a multi-slice fan beam collimator. IEEE Trans NucÃ-Sci 1979:26:610-618. 18. Ell PJ. Khan O. Emission computerized tomography: clinical applications. Semin NucÃMed 1981:11:50-60. 19. Billotey C, Aurengo A. Najean Y, et al. Identifying abnormal parathyroid glands in the thyroid uptake area using Tc-99m-sestamibi and factor analysis of dynamic structures. J NucÃ-Med 1994:35:1631-1636. 20. Coakley AJ, Kettle AG, Wells CP. et al. Technetium-99m-sestamibi: a new agent for parathyroid imaging. NucÃ-Med Commun 1989:10:791-794. 21. O'Deherty MJ, Kettle AG, Wells CP, et al. Parathyroid imaging with Tc-99msestamibi: preoperative localization and tissue uptake studies. J NucÃ-Med 1992:33: 313-318. 22. Geatti O. Shapiro B. Prolo G. et al. Location of parathyroid enlargement by Tc-99m-MIBI and 2U1T1scintigraphy, ultrasound and CT [Abstract]. J NucÃ-Med 1992:33:894. 23. Casara D, Rubello G, Saladini G, et al. Preoperative imaging of pathologic parathyroid glands (PG): comparison of Tc-99m-MIBI scintigraphy. Tl-201 scintigraphy. neck echography (NE), computed tomography (CT) and magnetic resonance (MR) [Ab stract]. Eur J NucÃ-Med 1992:19:684. 24. Sarfati E, De Ferron P, Gossot D, Assens P, Dubost C. Parathyroid adenoma: atypical sites ectopie or not? J Chir 1987;l:24-29. 25. Miller DL, Doppman JL. Shawker, et al. Localization of parathyroid adenomas in patients who have undergone surgery. Radiolog)- 1987:162:133-137. 26. Brennan MF, Doppman JL, Kurdy AG, et al. Assessment of techniques for preoper ative parathyroid gland localization in patients undergoing reoperation for hyperpara thyroidism. Surgen- 1982:91:6-11. 27. Aufferman W, Gooding GAW. Okerlund MD, et al. Diagnosis of recurent hyperpara thyroidism: comparison of MR imaging and other imaging techniques. Am J Roentgenol 1988:150:1027-1033.
Bone Scans in Neurofibromatosis: Neurofibroma, Plexiform Neuroma and Neurofibrosarcoma Richard T. Kloos, Vittoria Rufini, Milton D. Gross and Brahm Shapiro Division of Nuclear Medicine, Department of Internal Medicine, University of Michigan, and Department of Veterans Affairs Medical Centers, Ann Arbor, Michigan Neurofibromatosis type 1 or von Recklinghausen's disease is one of the most common autosomal dominant genetic disorders. Between 29% and 77% of patients may suffer from a wide range of skeletal abnormalities and, thus, patients with neurofibromatosis frequently undergo skeletal scintigraphy, at which time the common peripheral nerve soft-tissue tumors that occur in this syndrome (neurofibromas, plexiform neuromas and neurofibrosarcomas) may be demon strated. Methods: Single or multiphase 99nTc methylenediphosphonate (MDP) bone scans were performed in five patients with neurofibromatosis as part of their clinical evaluation. Results: We imaged neurofibrosarcomas in three patients, cutaneous neurofibromas in one patient and a plexiform neuroma in one patient. Conclusion: Single- or multiphasic bone scans may localize com mon soft-tissue tumors in neurofibromatosis.
Received Aug. 21, 1995; revision accepted Dec. 13, 1995. For correspondence or reprints contact: B. Shapiro, MB, ChB, PhD, University of Michigan Medical Center, Division of Nuclear Medicine, Box 0028, 1500 E. Medical Center Drive, Ann Arbor, Ml 48109-0028.
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Key Words: bone diseases; neurofibroma; neurofibrosarcoma; peripheral nerve neoplasms J NucÃ-Med 1996; 37:1778-1783
IN eurofibromatosis type 1 or von Recklinghausen's disease (1-4) is one of the most common autosomal dominant disor ders with a frequency rate of 1 in 3000 live births, an estimated prevalence of 30 patients per 200,000 population. This disease affects about 100,000 people in the United States with about 50% of cases representing new mutations (5-8). The gene responsible for its genesis has recently been mapped and cloned (9,10). Affected tissues include those of neuro-ectodermal, mesenchymal and endoderma! origins. The phenotypic mani festations are protean and may vary from no more than six cafe-au-lait spots 15 mm in diameter (5 mm in prepubescent patients) to amongst the most grotesque deforming lesions encountered in clinical medicine (5-7). The diagnostic criteria are listed in Table 1. The syndrome of bilateral acoustic
THE JOURNALOFNUCLEARMEDICINE• Vol. 37 • No. 11 • November 1996
TABLE 1 Diagnostic Criteria for von Recklinghausen's Disease (Neurofibromatosis Type 1)* Type 1
Genetic:
Cutaneous:
Ocular:
Skeletal:
(a) Identification of the presence of the gene. (b) One or more first degree relatives meeting the clinical criteria for diagnosis of neurofibromatosis 1. (a) Café-au-laitmacules, 6 or more with greatest diameter over 15 mm (5 mm in prepubescent children). (b) Two or more neuroflbromas of any type. (c) One or more plexiform neuromas. (d) Axillary or inguinal freckling. (a) Optic glioma. (b) Two or more hamartomas of the iris (Lisch nodules). (a) Distinctive sphenoid dysplasia. (b) Cortical thinning of long bones (with or without pseudarthrosis).
"Clinical diagnosis is made if a patient has positive proof of carrying the gene or manifests two or more of the clinical criteria [based on reference (11)]-
neuromas (neurofibromatosis type 2) should not be confused with von Recklinghausen's disease, as they are genetically distinct (5-7). There are rare cases of neurofibromatosis which share characteristics of both syndromes. Von Recklinghausen's disease is relatively common and 29%-77% of cases are associated with various with skeletal abnormalities (5,6,12-14) (Table 2). Consequently, patients with this disorder commonly are referred to nuclear medicine specialists for skeletal scintigraphy. In addition to the expected depiction of skeletal abnormalities (26), 99mTc methylenediphosphonate is taken up on three phase and delayed bone scintigraphy by a variety of soft-tissue lesions in von Reckling hausen's disease, including neurofibromas, plexiform neuromas and neurofibrosarcomas. Prior reports of such uptake have been TABLE 2 Typical Skeletal Lesions of von Recklinghausen's Neurofibromatosis Hypoplasia of the walls of the orbit (11,13) Calvarial defects: especially involving the parietal bones and left lambdoid suture (75-77) Kyphoscoliosis (both idiopathic type and a short, sharp angulating type involving 4-6 vertebral segments with associated vertebral and rib
FIGURE 1. Plexiform neuroma radiographie features (Patient 1). Note the extensive lobulated soft tissue masses, abnormal atrophie metacarpals and phalanges affecting the 3rd, 4th and 5th rays of the right hand.
sparse (27-29) and the phenomenon is listed are "rare" in a standard compendium of scintigraphic findings (30). METHODS Patients
Patient 1. A 34-yr-old man with neurofibromatosis, previous cosmetic facial surgery for disfiguring neurofibromas, right hand plexiform neuroma (Fig. 1) and thoracic kyphosis, devel oped an enlarging, painful, left forearm mass (17 cm). Fine needle aspiration (FNA) demonstrated neurofibrosarcoma. CT revealed significant soft tissue and bone destruction by the forearm mass. A 99mTc-MDPbone scan (Figs. 2, 3) excluded distant osseous metastatic disease in anticipation of an aboveelbow amputation. Pre-operative MR1 demonstrated a 6 cm paraspinal (C2-C5) mass confirmed by FNA to represent neurofibrosarcoma. Despite five cycles of palliative chemother apy with adriamycin, ifosfamide, mesna and external beam radiation therapy to the paraspinal mass, the disease progressed. Taxol therapy was initiated and fever, chills and night sweats with progressive forearm mass ulcération were accompanied by a foul smelling discharge. Those symptoms were present at the scheduled admission for the second cycle of therapy. The patient refused an above the elbow amputation. A follow-up CT demonstrated paraspinal mass enlargement and spinal canal
abnormalities) (11,13,14,16,18) Vertebral body erosion or scalloping (11,14,16,18) Spinal and cranial nerve foramina erosion or enlargement (11,16,18) Hypoplastic vertebral pedicles (79) Thoracic and lumbar meningocele (11,15,16) Hip and pelvic deformities (11,12,20) Costal scalloping, rib notching, and ribbon-like ribs (11,16,18,19) Greater and lesser sphenoid wing abnormalities (11,15,16) Macrocranium (Õ7,27 ) Zygomatic dysplasia (77) Mandibular and maxillary deformity (11,13,15,22) Long bone cortical dysplasia (78,27 ), metaphysial and diaphysial sclerosis (14), intramedullary linear sclerosis (23), subperiosteal hematoma (11,14,18), bowing (13,14,16,24), subperiosteal or cortical cystic lesions (11,13,14,21,24,25), pathological fracture (24), and pseudarthrosis (77,73,74,76,78) Localized or hemi-hypotrophy (77,73,14 ) Localized or hemi-hypertrophy (14,16,25)
• FIGURE 2. Technetium-99m-MDP three-phase bone scan (Patient 1). (A) Selected frames from the nuclear angiogram shows increased blood flow to plexiform neuroma of right hand and neurofibrosarcoma of left forearm (which has hyperemic rim and "cold" center) (arrows). (B) Marked increase in blood pool affecting the same regions.
BONESCANSIN NEUROFIBROMATOSIS • Kloos et al.
1779
l
B
B
V FIGURE 3. Technetium-99m-MDP bone scan delayed images (Patient 1). (A) Abnormal bone uptake in the 3rd, 4th and 5th metacarpals and extensive soft-tissue uptake in the plexiform neuroma of the hand. (B) Abnormal softtissue uptake in the soft-tissue neurofibrosarcoma of the forearm. Increased bone uptake in the proximal radius is due to direct tumor invasion.
invasion. Palliative measures were requested. Death soon there after was believed to result from diaphragmatic paralysis. Patient 2. A 45-yr-old female was diagnosed with CharcotMarie Tooth disease as a child and suffered progressive bilateral equinovarus deformity. This was treated with bilateral triple arthrodesis with a transfer of the anterior tibial tendons to the cuboid bones. She also had lifelong hand and lower extremity weakness, including bilateral foot drop, muscle atro phy and recurrent left patella dislocation. The female developed multiple neurofibromas at 16 yr of age and was diagnosed with neurofibromatosis at age 18 yr. She underwent multiple surgical resections of painful or disabling neurofibromas, including those from the ulnar nerves bilaterally, both hands, the right perilumbar area and the right forearm. There was long standing proptosis and exophthalmos. Right facial and trigeminal nerve neuromas caused right sided facial paralysis which led to multiple subsequent cosmetic and partial function restoring facial surgical procedures. Removal of a 7 cm by 10 cm right neck vagus nerve neurolemoma was complicated by right vocal cord paralysis. A three-phase 99mTc-MDP bone scan was
FIGURE 5. Technetium-99m-MDP bone scan after 3-hr delay (Patient 3). (A) Anterior and (B) posterior thigh views. Note the large area of irregular soft tissue tracer uptake involving the left thigh (arrow heads); there is no abnormality of the underlying bone.
reflexic. The patient likewise had bilaterally impaired vocal cord function and was experiencing shortness of breath. The patient underwent debulking of the cervical schwannoma with C1-C2 laminectomy and elective tracheostomy. Future surgical considerations include interventions aimed at the vocal cord dysfunction, the right trigeminal neuroma filling the ear and temporal bone, both acoustic neuromas and auditory brain stem implantation. The patient's form of neurofibromatosis
obtained to rule out a left ankle stress fracture (Fig. 4). Subsequent serial head and neck CT examinations demon strated the progressive appearance of a mass involving the right petrous bone, bilateral acoustic neuromas, multiple expanding intracranial meningiomas, a high cervical mass within the cervical canal with spinal cord compression at Cl and C2, left orbital schwannomas and trachéalcompression. The patient was rendered deaf, dysarthric, visually impaired and hyper-
currently been considered a variant of type 2. No family members have neurofibromatosis the patient does not have cafe-au-lait spots or Lisch nodules. The bilateral acoustic neuromas and extensive meningiomas are consistent with neu rofibromatosis type 2. Such patients may develop peripheral neurofibromas in the cervical region which are frequently large. Neurofibromas of the hands are also commonly observed. No definitive genetic studies are available regarding this patient. Patient 3. A 29-yr-old man with a family history of neuro fibromatosis, cafe-au-lait spots, status postresection of a medial left thigh plexiform neurofibroma 14 yr prior to evaluation and one other neurofibroma above the left eye was studied. Follow ing resection, the residual lesion slowly increased in size until rapid growth associated with an increasingly hard and irregular consistency, increased lesion pigmentation and mild pain with activity began 10 mo prior to evaluation. CT demonstrated the mass to be centered medially in the soft tissues and inseparable from the adjacent adductors with overall dimensions of 20 X 18X15 cm. Suspicion of right symphysis/inferior pubic ramus osseous metastatic disease prompted Tc-MDP bone scintigraphy (Fig. 5). Chest radiograph and CT demonstrated innu-
FIGURE 4. Technetium-99m-MDP bone scan (Patient 2). Anterior blood flow (A), pool image (B) and 3-hr delayed image (C). Note the intense patchy blood flow and focal blood-pool uptake in multiple cutaneous neurofibromas over the legs and ankles only some of which are visualized on the delayed image.
FIGURE 6. Posterior chest, abdo men and pelvic 99mTc-MDP bone scan in a 35-mo-old child with neu rofibromatosis and severe kyphoscoliosis (Patient 4). There is no tracer uptake in soft tissue neurofi bromas.
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THEJOURNAL OFNUCLEAR MEDICINE • Vol. 37 • No. 11 • November 1996
of the thoracic mass revealed many plexiform extensions which could not be excised. The sympathetic chain was invaded by tumor and soft-tissue infiltrations. Tissue pathol ogy diagnosed ganglioneuroma and ganglioneuroblastoma, and Shimada classification, including: stroma rich, nodular and intermediate differentiation (unfavorable histology). Surgery was complicated by left Horner's syndrome. Fol low-up neck, chest, abdominal and pelvic CT demonstrated a low attenuation mass which encased the celiac axis, superior mesenteric artery and splayed the pancreas and splenic vein. Bone marrow aspirate and biopsy, 24 hr catecholamines, ferritin, and 13II- and [123I]MIBG scintigraphy studies showed no abnormalities. A 99mTc-MDP bone scan showed
FIGURE 7. Anterior pelvic "TcMDP bone scan showing subtle soft tissue uptake overlying the region of the left sacroiliac joint (arrow heads) at the site of a retroperitoneal neurofibrosarcoma (Patient 5). There is no uptake by benign neurofibromas in the field of view.
merable widespread, and diffuse pulmonary nodules varying in size from several millimeters up to 5 cm. A core needle biopsy of the thigh mass demonstrated a malignant peripheral nerve sheath tumor (spindle cell) in association with neurofibroma consistent with a neurofibrosarcoma. Patient 4. A female infant was diagnosed with pulmonary valve stenosis at age 2 mo, > 20 cafe-au-lait spots noted at age 3 mo, axillary and inguinal freckling, neurofibromas and progressive kyphoscoliosis also beginning at age 3 mo. A thoracic, abdominal and pelvic CT scan at age 10 mo demon strated a left paraspinal thoracic mass at the point of levoscoliosis with a density of 34 Hounsfield units. A cervical, thoracic and lumbosacral MRI study demonstrated the mass to be 6 X 3 X 2 cm in diameter with heterogeneous enhancement and penetration of at least one neural foramina. Operative resection
no osseous metastatic disease. Biopsy of the celiac mass demonstrated ganglioneuroma. Serial follow-up bone scans (Fig. 6), MIBG studies and CT scans have not shown evidence of local progression or metastatic disease. Ortho pedic consultation documented rigid kyphoscoliosis and spinal bracing was instituted which she tolerated suboptimally. Despite careful follow-up, her curvatures progressed to 95°levoconvex thoracic kyphoscoliosis and 100°dextroconvex thoracolumbar scoliosis by 45 mo of age. Patient 5. A 23-yr-old woman was diagnosed at age three with a presumptively new mutation causing neurofibromatosis based on > 6 cafe-au-lait spots and Lisch nodules, with the subsequent development of multiple neurofibromas by age 16 (which increased in number during two subsequent pregnancies and oral contraceptive use), and a neurofibromatosis affected child with unaffected parents. During a prenatal visit, a left
TABLE 3 Radiopharmaceutical Uptake by Soft-Tissue Lesions in von Recklinghausen's Disease Radiopharmaceutical ""Tc-diphosphonates
[""Tcjpertechnetate "Tc-DTPA
Significance
References
Soft-tissue uptake noted in all types of lesions,
Current report (28 ) and (27) are the same case, (29,30)
Findings Uptake in neurofibromas, plexiform neuromas and neurofibrosarcomas.
perhaps more often in malignant tumors. Does not necessarily mean bone involvement.
Photon deficient subperiosteal hemorrhage with uptake in elevated periosteum. Uptake in neurofibromas and neurofibrosarcomas. Uptake in neurofibroma and plexiform neurofibroma. Uptake in neurofibromas, malignant schwannomas and plexiform neuromas.
(34) Tracer uptake occurs in both benign and malignant lesions. Avoid confusion with parotid gland tumors.
(35,36)
Scintigraphic uptake of "Tc-DTPA
(32,33,40-43)
is
(37-39)
analogous to Gd-DTPA used in nuclear magnetic resonance imaging. Uptake occurs in other soft-tissue pathologies and may
""Tc-sulfur
colloid
67Ga-citrate 131|*
Gallium uptake may distinguish malignant from benign lesions. Avoid false-positive diagnosis of functioning
Uptake in abdominal neurolemoma.
123lor[131l]MIBGt
Uptake in pheochromocytomas ordinary neurofibromas.
[18F]FDG
Uptake greatest in malignant lesions.
197Hg-chlormerodrin
reflect overall active fibroblast uptake. Abnormal lymphatic drainage depicted.
Dilated lymphatics and enlarged lymph nodes in elephantiasis neuromatosa. Uptake in neurofibrosarcoma.
but not in
Uptake in plexiform neurofibroma.
The same would probably be true of 123I. same would probably be true of 18F and radiobromine-labeled
thyroid cancer metastasis. MIBG uptake helps to distinguish pheochromocytoma from most neurofibromas. MIBG uptake has been reported in atypical schwannoma. Generally [18F]FDG uptake is greatest in malignant lesions. Normal uptake occurs in the nasopharynx, superior saggital sinus and parotid glands.
(44) (26,45) (46) Current report, (47,48)
(49) (39)
analogs.
BONESCANSIN NEUROFIBROMATOSIS • Kloos et al.
1781
lower quadrant abdominal mass was detected and subsequently characterized by CT and MRI as being 9 X 8 X 7 cm in size and medial to the left iliac wing displacing the abdominal muscu lature. The mass was heterogeneous in density with central low attenuation necrosis, irregularly contrast enhancing and without associated satellite lesions or lymphadenopathy. In retrospect, a prickling, burning, itching intermittent pain was experienced for 2 yr above the left knee which radiated to the left groin. This pain was relieved by left hip flexion and worsened by hip extension. Examination revealed weakness of the left leg with decreased left knee reflex and impaired sensation in the distri bution of the anterior femoral nerve. Needle aspiration cytology of the mass was nondiagnostic, while incisional wedge biopsy demonstrated a high grade neurofibrosarcoma arising within a benign neurofibroma. A 99mTc-MDP bone scan was obtain to
CONCLUSION Scintigraphic techniques have a significant role to play in the investigation of skeletal abnormalities and soft-tissue tumors in von Recklinghausen's neurofibromatosis. All three of the com mon peripheral nerve soft-tissue tumors that occur in this syndrome may show uptake of 99mTc-labeled bone-seeking radiopharmaceuticals on three-phase or delayed bone scintigra phy.
exclude osseous metastatic disease (Fig. 7). Chemotherapy and external beam radiation therapy were performed, and after partial tumor regression the patient underwent primary tumor resection without recurrence through 3.5 yr of follow-up obser vation.
1. Tiresius TC. Pathological investigation of an unusual deformity of the skin. Leipzig: S.L. Crusius; 1793. 2. von Recklinghausen FD. On the multiple fibromas of the skin and their relationship to multiple neuromas. In: Festschrift Fur Rudolf Virchon: Berlin: August Hirschwald; 1882. 3. Fulton JF. Robert W. Smith's description of generalized neurofibromatosis (1849).
DISCUSSION Many of the neurogenic
rumors in von Recklinghausen's
disease may show significant uptake of diphosphonate bone tracers. The increased vascularity and capillary permeability of the tumors in this study also resulted in some of the lesions showing tracer uptake on all three phases of the bone scan. In this respect, these lesions join the ever-growing group of tumors that manifest this phenomenon (which may or may not be associated with soft-tissue calcification either macroscopically or microscopically) (31 ). The sensitivity of scintigraphy with diphosphonate bone tracers to detect these soft-tissue tumors is not known (32,33). A wide range of radiopharmaceuticals have been employed for various purposes to study the soft tissues tumors of von Recklinghausen's neurofibromatosis (Table 3). In addition, the literature is extensive on the use of radioisotope brain scanning for acoustic neuromas which occur in neurofibromatosis type 2 and other central nervous system tumors which occur in both neurofibromatosis types 1 and 2 and which lie outside the scope of this study (15,50). The bone scan may be useful in the management of some of the skeletal abnormalities associated with neurofibromatosis (Table 2). This is particularly true for follow-up after surgical intervention (e.g., after surgical correc tion of scoliosis or in the evaluation of the healing of cortical defects following repair (perhaps including the placement for bone grafts). It has been reported that sarcomatous change in neurofibromas occurs in 2%-16.5% of patients (11,16,51). In attempting to distinguish between benign neurofibroma or plexiform neu roma and neurofibrosarcoma, gallium or [I8F]FDG avidity suggests malignancy (45,49). Pheochromocytoma occurs in l%-4% of patients with neurofibromatosis type 1 (47). The distinction of pheochromocytomas (and closely related neuroendocrine tumors) from neurofibromas has posed a major challenge for anatom ical imaging modalities. Iodine-131- or [123I]metaiodobenzylguanidine (MIBG), however, has proven efficacious in this task as neurofibromas ordinary are not MIBG-avid. The same would probably be true for related radiopharmaceuticals (e.g., "C-hydroxyephedrine and radio-Br or F-labeled analogs of MIBG). There are rare reports of MIBG uptake by atypical schwannomas (48). The role of radiolabeled somatostatin analogs (e.g., " ' In-octreoscan) in distinguishing pheochromocytomas from neurofibromas 1782
is similar to that of MIBG.
ACKNOWLEDGMENTS Supported in part by Cancer Research Training in Nuclear Medicine Grant NCI 2 T32 CA09015-19 and the Department of Veterans Affairs, Ann Arbor, MI. REFERENCES
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THE JOURNALOF NUCLEARMEDICINE• Vol. 37 • No. 11 • November
1996
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Quantitative Comparison of Planar and SPECT Normal Data Files of Thallium-201, Technetium99m-Sestamibi, Technetium-99m-Tetrofosmin and Technetium-99m-Furifosmin Hitoshi Naruse, Edouard Daher, Albert Sinusas, Diwakar Jain, Donna Natale, Jennifer Matterà , Robert Makuch and Frans J.Th. Wackers The Cardiovascular Nuclear Imaging Laboratory, Departments of Diagnostic Radiology, Medicine, Epidemiology and Public Health, Yale University School of Medicine, New Haven, Conneticut In recent years, several of ""Tc-labeied myocardial perfusion imaging agents have been developed, such as 99mTc-sestamibi, 99mTc-tetrofosmin and 99nTc-furifosmin. Although images obtained with these new tracers have a general similar appearance, there are differences in the myocardial kinetics, body distribution, general quality of images and imaging protocols. The aim of this study was to quantitatively compare normal exercise planar and SPECT data files obtained with 201TI and ""Tc-labeled agents. Methods: Lower-limit-of-normal curves were generated for each specific radiopharmaceutical from normal subjects with low (
