ASSESSMENT OF RADIOIODINE CLEARANCE IN PATIENTS WITH ...

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Radiation Protection Dosimetry Advance Access published May 4, 2012 Radiation Protection Dosimetry (2012), pp. 1–5

doi:10.1093/rpd/ncs063

ASSESSMENT OF RADIOIODINE CLEARANCE IN PATIENTS WITH DIFFERENTIATED THYROID CANCER Faraj Tabei1,2, Isa Neshandar Asli2, Zahra Azizmohammadi2, Hamid Javadi3 and Majid Assadi4,* 1 Department of Medical Physics and Engineering, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Department of Nuclear Medicine, Taleghani Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran 3 Golestan Research Center of Gastroenterology and Hepatology (GRCGH), Golestan University of Medical Sciences (GUOMS), Gorgan, Iran 4 The Persian Gulf Nuclear Medicine Research Center, Bushehr University of Medical Sciences, Bushehr 3631, Iran *Corresponding author: [email protected], [email protected]

Radioiodine (131I iodide) has long been a safe, effective and widely used treatment in the management of differentiated thyroid cancer (DTC). Concerns regarding stochastic radiogenic risks have led to regulatory criteria for the release from medical confinement of patients who receive such radionuclide therapy. Over a 6-y period, the external whole-body dose rates at 1 m from 562 DTC patients were measured with an ionisation chamber calibrated in microsieverts per hour out to 5-d post-administration. Patients were stratified into four administered activity groups: 3.7 GBq (36.8 %), 5.55 GBq (47.3 %), 7.4 GBq (12.8 %) and 9.25 GBq (3 %). Consistent with previously published data, the current study demonstrated that a bi-phasic model accurately described 131I-iodide kinetics up to at least 5-d post-administration in DTC patients, providing data that would be useful in formulating radiation safety guidelines for staff and other individuals coming into contact with such patients after treatment.

INTRODUCTION The medical use of unsealed radionuclides represents one of the important sources of population exposure from ionising radiation. During recent decades, the use of radiopharmaceuticals for therapeutic proposes has expanded worldwide(1 – 3). Radionuclide therapy has recently undergone further expansion owing to the introduction of new techniques and radionuclides(3 – 5). 131 I has long been used for the treatment of thyroid disorders such as hyperthyroidism and thyroid cancer(4). Because of the relatively high exposure rates in the proximity of patients who have received therapeutic amounts of radioiodine, regulations often require that such patients remain hospitalised until some regulatory criterion has been satisfied (e.g. the retained activity decreasing below a specified value)(5). Regulations for the release of patients treated with 131 I differ from country to country. In the USA, for example, such patients may be released provided the licensee can demonstrate that the doses to individuals with whom the patient may come in contact is not likely to exceed 5 mSv (0.5 rem) (US NRC Regulatory Guide 8.39)(6). However, the propriety of dose-based rather than activity-based release criteria for radionuclide therapy patients remains controversial(7 – 9). Taking into account the dose limits and constraints recommended by the International

Commission on Radiological Protection (ICRP), regulations in some countries rely on using the retained activity or the dose rate as a release criterion(10). More specifically, measurement of a patient’s dose rate at a fixed distance has been used as a discharge criterion in some countries(11 – 16). In the current study, the authors used the dose rate of patients at a fixed distance (1 m) for the modelling of radioiodine clearance from thyroid cancer patients. Better characterisation of the time-dependent change in the exposure rate would aid radiation safety decision-making. Prior studies suffered from small sample sizes and/or limited numbers of measurements(17 – 19). The purpose of the current study, therefore, is to assess the time-dependent exposure rate post-administration of therapeutic radioiodide to a large number of differentiated thyroid cancer (DTC) patients and to identify a mathematical function that reliably represents these data. MATERIALS AND METHODS Participants and study design This prospective study recruited 562 patients over a period of 6 y, from 2005 to 2010. All enrolled patients had a history of DTC. Patients were evaluated for the surgical and pathological status, status of the DTC at

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Received November 12 2011, revised March 28 2012, accepted April 3 2012

F. TABEI ET AL.

received 5.55 GBq (150 mCi); 72 (12.8 %) received 7.4 GBq (200 mCi) and 17 (3 %) received 9.25 GBq (250 mCi). In total, 441 (78.5 %) of patients were released after 3 d; 487 (86.7 %) after 4 d and 545 (97 %) after 5 d. There were 17 (3 %) with a hospitalisation period of .6 d, owing to functional thyroid remnants and widespread metastases. The mean release time post-administration was 3.41+0.95 d. A bi-exponential formula was fit to the time-activity data for all groups, with a fast clearance phrase initially followed by a slower clearance phrase (Figure 1). The dose rates at 1 m for the four administeredactivity groups , DR100, DR150, DR200 and DR250, are given as a function of time in Equations (1 –4), respectively DR100 = 163.44 e1:41t + 5.24 e0:43t

ð1Þ

DR150 = 179.50 e1:83t + 59.12 e0:55t

ð2Þ

DR200 = 186.31 e2:24t + 142.71 e1:38t

ð3Þ

DR250 = 194.36 e2:77t + 217.52 e2:09t

ð4Þ

where DRX is the dose rate (in mSv h21) at time t post-administration (in hour) in the patient group administered X mCi of 131I. The effective half-life in the 3.7 GBq group was 11.76 h at the initial phase and 38.64 h at the final phase; by considering the physical half-life, the biological half-lives were calculated to be 12.52 and 48.37 h, respectively. The effective half-life (Te) and biological half-life (Tb) of the initial and final phases of the respective bi-exponential functions are shown

RESULTS A total of 562 patients (440 females and 122 males) with a mean age+SD of 36.6+11.20 y took part in the study. In total, 500 patients had the papillary type of differentiated thyroid cancer, 51 cases had the follicular type of DTC and 11 cases had the Hurtle cell type. At the initial operation, 532 patients underwent total thyroidectomy and the remaining 30 patients had near-total thyroidectomies. The administered activity ranged from 3700 to 9250 MBq (100–250 mCi). A total of 207 (36.8 %) patients received 3.7 GBq (100 mCi); 266 (47.3 %)

Figure 1. The variation of the dose rate as a function of time for four administered-activity groups: 3.7 GBq (100 mCi), 5.55 GBq (150 mCi), 7.4 GBq (200 mCi) and 9.25 GBq (250 mCi).

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the time of the initial surgery, extent of metastasis at the time of radioisotope scintigraphy, subsequent operations, clinical findings and serum thyroglobulin and thyroid-stimulating hormone (TSH) levels. The inclusion criteria also included a negative human chorionic gonadotrophin measurement in women to avoid radioiodine administration to pregnant females, total or near-total thyroidectomy one month or longer from the administration of radioiodine therapy, the absence of additional pathology (such as renal dysfunction) and, finally, an informed consent form signed by the patient (7). Patients were carefully questioned about any exposure to exogenous iodine before scanning and all patients were advised to avoid medication containing iodine during the preparation time for the diagnostic scan. The treatment was performed after stopping levothyroxine for one month and liothyronine for 2 weeks. At the time of treatment, all patients had serum TSH levels above 30 mIU l21. The interval between the total thyroidectomy and initial radioiodine therapy was ,2 months in all patients. The post-therapy scans were performed just before the patient was released following 131I therapy. Patients were stratified into four administered activity groups: 3.7 GBq (36.8 %), 5.55 GBq (47.3 %), 7.4 GBq (12.8 %) and 9.25 GBq (3 %). The external whole-body dose rates of patients were measured at a distance of 1 m using a radiation-detection survey meter with an ionisation chamber [Geiger (GM5C plus) Counter, Graetz, Germany] calibrated in microsieverts per hour. For each measurement, the maximum dose rate of the neck and upper trunk portion of the patient’s body was recorded. All dose rate measurements were done after bladder emptying by the patients and also subtraction of background dose rates. The post-therapy dose rate measurements were performed daily until the dose rate fell below the release-criterion value, 10 mSv h21 (1.0 mR h21) at a distance of 1 m. This study was approved by the institutional ethics committee of Shahid Beheshti University of Medical Sciences. The data were analysed by Microlab Origin Prom Version 6 (Northampton, USA).

RADIOIODINE CLEARANCE IN DTC Table 1. Effective and biological half-lives at the initial and final phases in four administered-activity groups. Administered activity (GBq)

3.7 5.55 7.4 9.25

Initial phase

Final phase

Te(hour)

Tb(hour)

Te(hour)

Tb(hour)

11.76 8.88 7.42 6.00

12.52 9.31 7.72 5.22

38.64 30.24 12.05 7.95

48.37 35.89 12.85 8.29

Te, effective half -life; Tb, biological half-life.

DISCUSSION Surgical resection followed by radioiodine (131I iodide) ablation has long been the standard treatment for DTC. The effective half-time for the totalbody clearance of radioiodine is normally 5.5 d (132 h) but is much shorter in post-thyroidectomy DTC patients(20). The assessment of the external exposure or the dose rate in patients treated with radioactive materials is one of the established methods of estimation of radioactive body burden(17, 20 – 22). Thomas et al.(23) assessed three methods of the estimation of the radiation exposure, which were a urine assay, prediction based on a pre-therapy diagnostic workup method using 74 MBq and external exposure-rate measurements. They concluded that the direct external exposure rate method was an accurate, reliable and safe method of monitoring the patient’s 131I body burden. In our study, the time-dose rate data for each of the four administered-activity groups followed a bi-exponential function. Accordingly, there is rapid total-body clearance of radioiodine on the first day post-administration, with slower clearance subsequently. Specifically, the clearance constants of both the initial and final components increase progressively as the administered activity is increased from 100 to 250 mCi. Likewise, the fraction of the total-body activity cleared by the faster initial component decreases progressively as the administered activity is increased from 100 to 250 mCi. This finding is in agreement with the results of several other studies(8, 13, 16, 17, 24). The initial rapid clearance likely corresponds to urinary excretion of inorganic iodine (iodide), whereas the second slower clearance corresponds to the catabolism of organified radioiodine and its subsequent excretion, although the organification of radioiodine is minimal in athyreotic (i.e. post-

CONCLUSION The current study demonstrates that a bi-phasic model accurately describes 131I-iodide kinetics up to at least 5-d post-administration to DTC patients,

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in Table 1 for the four administered-activity groups. The time-dose rate data for each of the four administered-activity groups and the respective bi-exponential fits are shown in Figure 1.

thyroidectomy) patients(25, 26). Barrington et al.(17) assessed whole-body dose-rate measurements in 86 thyroid cancer patients after radioiodine administration. The dose-rate decay was bi-exponential for patients taking 131I to ablate the thyroid after surgery and the mean half-lives (+1 SD) of the short and long components of the dose rate decay were 0.50 (+0.09) and 4.28 (+1.55) d, respectively, but monoexponential for patients receiving subsequent treatments for residual or recurrent disease with a mean half-life of 0.75+0.01 d at 1 m. The faster clearance in the follow-up patients may be due to a lesser quantity of functioning thyroid tissue. Also, these patients were a heterogeneous group, who had undergone a variety of surgical procedures; some patients had undergone a lobectomy only and had significant thyroid remnant tissue. In contrast, all our patients had a total or near-total thyroidectomy. This may explain the same bi-exponential model applying to all the patients analysed in the current study. Sasikala et al. performed the dose-rate measurements in 23 DTC patients after radioiodine administration. Measurements were performed at 1, 3, 5, 8, 24, 48 and 72 h post-radioiodine administration. They deduced a tri-exponential clearance pattern(27). A similar study by Castronovo et al.(28) also revealed a tri-exponential clearance pattern, comprising a rapid initial component and two delayed components with biological half-times (T1/2biol) of 7.5, 41 and 52 h, respectively. Another study by Thomas et al. suggested that whole-body retention is generally characterised by an initial fast phase (with an effective half-life of 11 h) and a longer half-time becoming apparent beyond 60-h post-radioiodine administration(23). Different clearance models of radioiodine in patients with DTC may be related to differences in the numbers and times of post-therapy measurements, patient populations and sample sizes among the foregoing studies. The mean effective half-time and biological halftime in the current study are consistent with previously reported values(17, 22). Our study indicates a strong dependency of T effective on the biologic half-life and the results for T1/2bio are in considerable agreement (17.4 h) with the previous reports. A study by the European Commission revealed that around 80 % of the radioactive burden should be eliminated within 48 h with T1/2bio of ,0.96 d(15). Another paper showed that, for most patients, 35 –75 % of the administered dose is eliminated within the first 24 h after dosing(29), consistent with the T1/2bio values in the 0.5– 2.0 d range.

F. TABEI ET AL.

providing data that would be useful in formulating radiation safety guidelines for staff and other individuals coming into contact with such patients after treatment. FUNDING

12. 13.

This study was sponsored by Shahid Beheshti University of Medical Sciences (grant no. 38762).The authors extend their thanks to colleagues at the institutes for their technical help and assistance with data acquisition. CONFLICT OF INTEREST

14.

15.

16.

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The author(s) declare that they have no competing interest.

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