Radiation Safety Precautions in 131 I Therapy of Graves Disease Based on Actual Biokinetic Measurements

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1 ORIGINAL ARTICLE Radiation Safety Precautions in 131 I Therapy of Graves Disease Based on Actual Biokinetic Measurements Bin Liu,* Rong Tian,* Weiai Peng, Ying He, Rui Huang, and Anren Kuang Departments of Nuclear Medicine (B.L., R.T., W.P., R.H., A.K.) and Ultrasonography (Y.H.), West China Hospital, Sichuan University, Chengdu , China Context: Radiation protection is an integral part of targeted radionuclide therapy. How to offer rational radiation precautions to patients with Graves disease (GD) undergoing 131 I therapy is still a matter of ongoing discussions. Objective: The objective of the study was to formulate radiation precautions for GD patients undergoing 131 I therapy through actual biokinetic measurements for a particular population of patients. Design: This was a prospective study. Setting: The study was conducted at a university hospital. Patients: From January 2009 through January 2012, consecutive GD patients prepared for 131 I therapy were prospectively recruited. Main Outcome Measures: Pretherapy thyroid radioiodine uptake and uptake ratio (4 to 24 h radioiodine uptake) were measured. Serial whole-body dose-rate measurements after therapy were performed to deduce 131 I whole-body retention. Calculations based on deduced whole-body retention and measured thyroid radioiodine biokinetics were derived to determine the thyroidal and extrathyroidal compartment uptake fractions and effective half-lives. Precaution times necessary to avoid close contact with family members and the general public were derived from these parameters and regulatory dose limits. Results: A total of 72 patients were eligible for the analysis. A high interpatient variability in 131 I biokinetics was observed: the mean peaking 131 I uptake ( 1 SD) in the thyroid was 68% ( 19%), and the range was 18% 89%; the mean effective 131 I half-life ( 1 SD) in the remainder of the body was 5.1 ( 0.9) hours (range h). The mean measured initial dose rate ( 1 SD) at 1.0 m after 131 I administration was ( 0.003) Sv h 1 MBq 1 (range Sv h 1 MBq 1 ). The 0.3:1.0 m initial dose rate ranged from 2.9 to 7.1, which was greatly lower than the projected ratio of 11.1 by the inverse square law approximation. On the basis of the measured radioiodine biokinetics and dose rates, detailed instructions were provided to limit nearby individuals exposure. Conclusion: The use of actual biokinetic measurements may remove the effect of variability errors associated with general default assumptions about the 131 I biokinetics in GD patients. The marked variability in 131 I biokinetics among GD patients reinforces the need for patient-specific iodine biokinetic measurements for radiation safety precautions. (J Clin Endocrinol Metab 100: , 2015) ISSN Print X ISSN Online Printed in USA Copyright 2015 by the Endocrine Society Received March 17, Accepted June 1, First Published Online June 5, * B.L. and R.T. contributed equally to the present study. Abbreviations: DE, dose equivalent; EDE, effective DE rate; GD, Graves disease; IDR, initial dose rate; TEDE, total EDE; T eff, expected effective half-life 131 I in the thyroid; U 4h, uptake at 4 hours; U 24h, uptake at 24 hours press.endocrine.org/journal/jcem J Clin Endocrinol Metab, August 2015, 100(8): doi: /jc

2 doi: /jc press.endocrine.org/journal/jcem 2935 Radioactive-iodine 131 I therapy has proven to be an effective, cost-effective, and safe therapy for patients with hyperthyroidism due to Graves disease (GD) (1). This therapy is usually prescribed on an outpatient basis, and it is thus necessary to consider nearby individuals exposure doses and formulate radiation precautions to minimize the potential radiation to nearby individuals. Over the past few decades, several studies have attempted to formulate radiation precautions in 131 I therapy of GD (2 14). The suggested restrictions on patient behavior vary substantially in the published literature (10, 13). This is owing to several factors, including the lack of comprehensive investigation about iodine biokinetics in GD patients and varying methods for formulating radiation precautions. Patient-specific iodine biokinetics is one of important factors in determining nearby individuals cumulative doses and formulating radiation precautions. Due to the complexities of the procedures, few centers have offered precautions to GD patients based on individual measurements of the patient s iodine biokinetics. However, the validity of using the actual measured biokinetics in calculating cumulative doses and formulating radiation precautions has been demonstrated in radioimmunotherapies (15 17) and 131 I thyroid cancer therapy (18). The present study was undertaken to formulate radiation precautions for GD patients undergoing 131 I therapy through actual biokinetic measurements for a particular population of patients. Materials and Methods Patients Consecutive patients with a recent diagnosis of GD, submitted to their first 131 I therapy in our department during the period of January 2009 through January 2012, were prospectively enrolled in this study. The diagnosis of GD of all patients was based on the standard clinical criteria: elevated thyroid hormone levels, suppressed thyrotropin, positive thyroid-simulating antibody, diffuse goiter, and high radioiodine uptake. Exclusion criteria included age below 18 years, suspicion of pregnancy, the presence of any suspicious thyroid nodule on ultrasound examination, active moderate to severe or sight-threatening ophthalmopathy, and large and compressive goiters. Before therapy administration, each patient underwent a full clinical evaluation, determination of thyroid volume by highresolution ultrasound examination and always being performed by the same ultrasound-experienced physician, 4-hour (U 4h ) and 24-hour (U 24h ) thyroid radioiodine uptake measurements, and thyroid 99m Tc-pertechnetate scintigraphy. This prospective study was approved by our institutional review board. Each patient signed a consent form after receiving an explanation of study aims. Treatment protocol All patients were instructed to stay on a low-iodine diet for at least 2 weeks before thyroid radioiodine uptake measurements. Antithyroid drugs (methimazole) were withdrawn at least 3 days before measurements to avoid negative effects on radioiodine uptake and were restarted at the earliest 3 days after 131 I administration. Based on gland size and uptake, the administered activity was calculated as follows: A M (100/U max ) C. In this formula, where A is the 131 I activity in megabequerels, M the thyroid mass (grams) determined by ultrasonography via using the ellipsoid formula and assuming a mass density of 1 g ml 1,U max was the maximum fractional thyroid uptake in percentage (whether it is U 4h or U 24h ), and C was a constant representing the activity projected per unit of thyroid tissue mass (megabequerels per gram 1 ). For patients with adverse effects of antithyroid drugs and other medical problems in which a decision was made to achieve a hypothyroid state, C was set at 7.4 MBq g 1.Inall other patients, C was 3.7 MBq g 1. Appropriate radiation safety measures were used to comply with provincial and state regulations regarding monitoring, waste handling, and patient release. Thyroid 131 I biokinetics Thyroid radioiodine uptake measurements were performed 4 hours and 24 hours after the administration of a tracer activity of 0.37 MBq 131 I, starting the day before 131 I therapy. All measurements were carried out with a thyroid uptake probe (Canberra 7350-PE collimator with a 2 2 NaI crystal) in conjunction with an anthropomorphic perspex neck phantom. The probe was positioned at a fixed distance of 28 centimeters from the patient s thyroid or neck phantom for 2 minutes. Three independent acquisitions were done for each counting and averaged. Measurements were corrected from room and patients background (ie, thigh). Quality assurance and quality controls were performed on a regular basis. The fractional thyroid uptake was determined with the following formula: 131 I uptake [(neck counts background thigh counts)/(standardcounts background room counts)] 100% (19). Based on a priori assumptions derived from literature data for the expected effective half-life (T eff )of 131 I in the thyroid of the individual patient with GD and the measured U 4h and U 24h in the study, the T eff values used in this study were considered as follows (20): normal kinetics, T eff 121 hours (T max 24 h, U 24h /U 4h 1.0); normal kinetics with quick uptake, T eff 121 hours (T max 4 h, 0.88 U 24h /U 4h 0.92); quick kinetics, T eff 107 hours (T max 4h,U 24h /U 4h 0.88); slow kinetics, T eff 169 hours (T max 4h,U 24h /U 4h 0.92), where T max is the time to maximum activity. Whole-body dose-rate measurements Whole-body dose rate measurements were conducted 0.5 (before any urinary elimination), 12, 24, 48, 96, and 168 hours after therapy administration of 131 I as liquid. All measurements were obtained at 0.3 m and 1 m from the upright patient. The initial dose rate (IDR; defined as the whole body dose rate measured before any activity excretion) was measured from the anterior midtrunk of the patient. The dose rates at subsequent time points were measured at the level of the patient s thyroid. Three readings were taken for each measurement and averaged. The survey instrument was a calibrated ionization chamber (RAMDA 2000-

3 2936 Liu et al Radiation Safety in 131 I Therapy of Graves Disease J Clin Endocrinol Metab, August 2015, 100(8): IC10-A probe; Rotem), which was source checked and corrected for ambient radiation levels before each measurement. These time-dependent whole-body dose rates were fit by minimizing the 2 and used to deduce nonphysical decay-corrected whole-body activity retention (17). The IDR obtained at 1 m was converted to be the baseline quantification with 100% of the administered activity. At this distance, the dose-rate measurements were not as strongly affected by the source spatial distribution (21). Subsequent measurements would give an indication of the residual activity. In 131 I therapy of GD, a good intraindividual agreement on thyroid iodine uptake has been documented between testing and therapy (22). As such, we used testing measurements to predict thyroid iodine uptake during therapy. By combining data on whole-body retention and data on thyroid iodine uptake, activity that was not in the thyroid (ie, was in the remainder of the body) was calculated and modeled by an exponential clearance function. The effective half-life in the remainder of the body was then determined by using the fit to the exponential function. Calculation of the total effective dose equivalent (DE) As presented by the National Council on Radiation Protection and Measurements report number 155 (23), the effective DE rate (EDE) at an index distance r (meters) from a GD patient at time t (hours) after 131 I administration can be modeled and calculated by using two components and five parameters as described by equation 1: t T EDE IDR r F i e ei (1) i 1 where EDE is the effective DE rate (millisievert per hour 1 ), IDR (r) the IDR (millisievert per hour 1 ) at an index distance r (meters) from the patient, F i the 131 I uptake fractions in the thyroidal (ie, the thyroid tissue) and extrathyroidal (ie, the remainder of the body) components, and the effective 131 I half-lives (hours) in the thyroidal and extrathyroidal components, and t the time (hours) after 131 I administration. In case of 131 I therapy, internal doses due to contamination are an order of magnitude less than external doses, and internal contamination doses could thus be neglected (24). On the basis of external exposure only, the total effective DE (TEDE) to an individual exposed to the patient from time t (hours) after administration to infinite time of exposure can be calculated as follows (23, 25): t T TEDE 1.44E r IDR r F i T ei e ei (2) i 1 where TEDE is the total effective DE (millisievert), E(r) the exposure factor and defined as the fraction of time that a person spends at a distance r (meters) from the patient, and the other parameters as defined for equation 1. Radiation safety precautions Regulatory dose limits The current US Nuclear Regulatory Commission criteria for patient release are based on limiting the TEDE to 5 msv for the maximally exposed individual (26). The use of the 1 msv limit for members of the general public, children, and pregnant women is recommended by the National Council on Radiation Protection and Measurements (23). Exposure factor (r) The following exposure factors were used in the current analysis (3, 13, 23): E (0.3 m) 0.33 for the patient s sleeping partner, assuming the sleeping partner spends 8 h/d at a distance of 0.3 m from the patient; E (1 m) 0.25 for a member of the patient s household, assuming a household member typically spends 6 h/d at a distance of 1 m from the patient; and E (1 m) 0.33 for a coworker of the patient, assuming the coworker spends 8 h/d at a distance of 1 m from the patient. Restricted periods Beginning with a t value on 0 hours and substituting t values in 24-hour increments (ie, 24, 48, 72 h... ), the smallest t value that yielded a value on the right side of the equation 2 equaled to or less than the maximum permissible TEDE of the respective cohort was the restricted period. Duration of public traveling As for limitation of public traveling, it was assumed that when a patient travels by public transportation, a fellow passenger sits at a distance of 0.3 m from the patient (13). The maximum permissible public traveling time in each day after 131 I administration was calculated as follows: t T 1mSv 1.44 IDR 0.3m F i T ei e ei (3) where x is the daily fraction time corresponding to the maximum permissible public traveling for each t (t 0, 24, 48, 72 h), IDR (0.3 m) the IDR (millisievert per hour 1 ) at 0.3 m from the patient and the other parameters as defined for equation 1. The precaution times to limit close contact with others were calculated for individual patients on the basis of the measured iodine biokinetics. In view of potential difficulties in measuring the patient s individual biokinetics in a busy clinic, using a population-specific iodine biokinetic model with fixed parameters can facilitate the calculation of nearby individuals radiation doses and formulation of simplified and consistent radiation precautions for GD patients after 131 I therapy. The upper 95th percentiles of IDRs, the thyroidal component uptake fractions, and the extrathyroidal component effective half-lives derived from the entire patient population were extracted to fit a population-specific iodine biokinetic model for GD patients. On considering that individual suboptimal biokinetic data collection was the procedure used to derive the thyroid effective half-lives and to avoid a possible underestimate of exposure doses, the maximum value of the derived thyroid effective half-lives in the study was selected to construct the iodine biokinetic model. Based on the fitted iodine biokinetic model and current regulatory limits, the radiation precautions for GD patients were formulated. Statistical analysis The Wilcoxon signed rank test was used to assess the differences between two quantitative variables. A value of P.05 was i 1

4 doi: /jc press.endocrine.org/journal/jcem 2937 considered to indicate a significant difference. The statistical analysis was performed with software (SPSS, version 17.0; SPSS Inc). Results Study cohort Ninety-five consecutive patients were approached for consent, and 78 consented. Six patients were excluded because of protocol violations, primarily due to technical problems during whole-body dose rate measurements. The remaining 72 patients constituted our patient population. Twenty-two patients (31%) were treated with antithyroid drugs before 131 I therapy. The mean thyroid mass ( 1 SD) was estimated at 43 ( 29) g (range g). The mean activity ( 1 SD) administered to all was calculated at 310 ( 267) MBq (range MBq). Details on patient characteristics are given in Table 1. Initial dose rate The mean IDRs ( 1 SD) at 0.3 m and 1 m were ( 0.021) Sv h 1 MBq 1 (range Sv h 1 Table 1. Baseline Characteristics and Iodine Biokinetics of 72 Patients With Graves Disease Treated by 131 I Parameter Value Patients, n 72 Gender, n, % Women 55 (76) Men 17 (24) Age, y Women (20 67) Men (19 59) P value a Weight, kg (42 78) Height, cm ( ) BMI, kg/m ( ) Thyroid mass, g (20 91) TR-Ab, IU/L (0.9 40) TR-Ab positive, n, % 59 (82) Ophthalmopathy, n, % Yes 35 (49) No 37 (51) ATD before 131 I, n, % Yes 22 (31) No 50 (69) Hormone levels before 131 I TSH, IU/mL ( ) FT 4, pmol/l (25 51) U 4h,% (15 86) U 24 h,% (18 89) Activity administered, MBq ( ) Abbreviations: BMI, body mass index; TR-Ab, thyroid-stimulating hormone receptor antibody; ATD, antithyroid drugs; FT 4, free T 4. Values are given as mean SD (range). Normal ranges are as follows: TR-Ab less than 3.0 IU/L; TSH, IU/mL; FT 4, pmol/l. a Using the Wilcoxon rank sum test. MBq 1, the upper 95th percentile value, Sv h 1 MBq 1 ) and ( 0.003) Sv h 1 MBq 1 (range Sv h 1 MBq 1, the upper 95th percentile value, Sv h 1 MBq 1 ), respectively. As can be seen, the mean ratio ( 1 SD) of the actual measured IDRs at 0.3 m to IDRs at 1.0 m was 4.6 ( 2.3) (range ). 131 I biokinetics The mean fractional thyroid uptakes ( 1 SD) were 55% ( 21%) (range 15% 86%) and 63% ( 15%) (range 18% 89%), respectively, at 4 and 24 hours. The uptakes peaked at 4 and 24 hours in 23 (32%) and 49 (68%) patients, respectively. The mean peaking uptakes ( 1 SD) in the thyroid were 68% ( 19%) (range 18% 89%; the upper 95th percentile value: 82%). On the basis of the uptake ratio of U 4h to U 24h, 5 (7%), 54 (75%), and 13 (18%) patients had the derived thyroid effective 131 I half-lives of 107 hours, 121 hours, and 169 hours, respectively. The mean effective 131 I half-life ( 1 SD) in the remainder of the body was 5.1 ( 0.9) hours (range h, the upper 95th percentile value, 6.9 h). Radiation safety precautions Patient-specific precautions The precaution times to limit close contact with others for individual patients on the basis of the measured iodine biokinetics are presented in Table 2. Over the range of administered activities of MBq of 131 Iinthe study, no precautions were needed for nonpregnant adult family members who do not sleep with the patient. By comparison, children and pregnant women who sleep with the patient were subject to the most restrictive precautions. The median times to avoid sleeping with pregnant women and children and nonpregnant adult family members were 14 (range d) and 2 days (range 0 12 d), respectively. Model-based precautions The parameters of the fitted population-specific iodine biokinetic model are presented in Table 3. On the basis of the fitted iodine biokinetic model and current regulatory limits, the precaution times for GD patients over the range of potential administered activities of MBq of 131 I are calculated (Tables 4 and 5). Discussion In dose calculations, activity distribution within a radioactive patient is generally assumed to be unattenuated point source, and the dose to nearby individuals at a given distance is therefore calculated by the inverse

5 2938 Liu et al Radiation Safety in 131 I Therapy of Graves Disease J Clin Endocrinol Metab, August 2015, 100(8): Table 2. Recommended Times to Avoid Contact With Others After 131 I Therapy and Maximum Permissible Times to Use Public Transportation on the Day of 131 I Therapy on the Basis of Measurements of the Patient s Individual Iodine Biokinetics Time Behavior (Median Values and Range) Sleep with nonpregnant adult family member for 8 h/d at 0.3 m a 2 (0 12) b Sleep with pregnant woman, infant, or child for 8 h/d at 0.3 m c 14 (12 28) b Contact with nonpregnant adult family member for 6 h/d at 1 m a 0 Contact with pregnant woman, infant, or child for 6 h/d at 1 m c 1 (0 7) b Contact with coworker or public member for 8 h/d at 1 m c 2 (0 10) b Daytime contact with nonpregnant adult family member for 6 h/d at 1.0 m, followed by 3 (0 12) b nighttime sleeping for 8 h/d at 0.3 m a Daytime contact with pregnant woman, infant, or child for 6 h/d at 1.0 m, followed by nighttime 16 (13 29) b sleeping for 8 h/d at 0.3 m c Use of public transportation on the day of administration c 11 (3 24) d a Calculated using dose of 5 msv. b Values are days. c Calculated using dose of 1 msv. d Values are hours. square law approximation (13, 26, 27). The use of a direct dose-rate measurement on each patient in our study facilitates the evaluation of the variability of patient dose rates and provides a basis for evaluating default assumptions about 131 I distribution in GD patients. In the study, the ratios of the actual measured IDRs at 0.3 m to IDRs at 1.0 m ranged from 2.9 to 7.1 (mean 4.6), which were greatly lower than the projected ratio of 11.1 by the inverse square law approximation. This finding was verified by a patient-specific dosimetric study by Rutar et al (15) in which actual dose-rate measurements were obtained on patients receiving radioimmunotherapies for non-hodgkin s lymphoma. In this study, the 0.3 m to 1 m IDR ratio ranged from 1.4 to 6.7 (mean 3.1). Our finding, interpreted together with the study by Rutar et al and measurements obtained on thyroid cancer patients after 131 I therapy (18) indicated that the use of a point-source simplification in 131 I therapy of GD would overestimate the dose rates by a substantial amount at the closer distances. A high interpatient variability in 131 I biokinetics was found in the study. The observed maximum fractional thyroid 131 I uptakes ranged from 18% to 89% (mean 68%). This finding was in good agreement with several prospective studies of 131 I uptake in the thyroid of GD Table 3. Fitted Iodine Biokinetic Model for Patients With Graves Disease Thyroidal Component Extrathyroidal Component IDR, Sv h 1 MBq 1 F 1 T e1 (h) F 2 T e2 (h) 1 m 0.3 m 0.8 a a a Values have been rounded. patients (28, 29). On the basis of the uptake ratio of U 4h to U 24h rather than on an individual basis, the thyroid effective 131 I half-lives were derived in the study. This method, being applied in the treatment planning of GD for dosimetric purposes, has been considered acceptably accurate and easily applicable (30). The derived thyroid effective half-lives in the study were in the range of the values reported in several studies reliant on large patient data sets and sequential 131 I uptake measurements (31, 32). As for the iodine clearance from the extrathyroidal tissues, our study demonstrated increased iodine clearance in GD patients. The mean effective 131 I half-life (5.1 h) in the extrathyroidal component observed in the study was lower than that (7.7 h) observed in normal subjects (33). This alteration may result from an increased glomerular filtration rate in hyperthyroidism because the kidney contributes to the iodine clearance primarily through glomerular filtration (34). The marked variability in 131 I biokinetics among GD patients reinforces the need for patient-specific iodine biokinetic measurements for radiation safety precautions. A wide range of patient-specific precaution times was identified in the study, which was due in large part to the variability in activity administered and the variability in individual 131 I biokinetics. Our results indicated that no precautions were needed for nonpregnant adult family members that do not sleep with the patient over the range of administered activities of MBq of 131 I. Children and pregnant women classified as critical groups were subject to the most restrictive precautions. In 131 I therapy of GD, a substantial amount of 131 I decaying within the patient body did so within the thyroid. A high level of 131 I uptake and a long effective half-life in the

6 doi: /jc press.endocrine.org/journal/jcem 2939 Table 4. Restricted Periods (Days) for Contacting With Others After 131 I Therapy on the Basis of the Fitted Iodine Biokinetic Model Administered Activity, MBq Behavior Sleep with nonpregnant adult family member for 8 h/d at 0.3 m a Sleep with pregnant woman, infant, or child for 8 h/d at 0.3 m b Contact with nonpregnant adult family member for 6 h/d at 1 m a Contact with pregnant woman, infant, or child for 6 h/d at 1 m b Contact with coworker or public member for 8 h/d at 1 m b Daytime contact with nonpregnant adult family member for 6 h/d at m, followed by nighttime sleeping for 8 h/d at 0.3 m a Daytime contact with pregnant woman, infant, or child for 6 h/d at 1.0 m, followed by nighttime sleeping for 8 h/d at 0.3 m b a Calculated using dose of 5 msv. b Calculated using dose of 1 msv. thyroid implied that body burden would be slowly cleared and the effective DE rate from the patient would be gradually decreased after 131 I administration. As a result, prolonged restricted periods were required for keeping the doses to pregnant women and children below 1 msv. Except the patient-specific iodine biokinetics, it has to be mentioned that the patient s physical and psychological conditions to comply with precautions, as well as individual living conditions, should also be taken into account in determining the actual radiation safety precautions for each patient. On considering the potential difficulties in measuring the patient s individual iodine biokinetics, especially effective 131 I half-lives, in a busy clinic, we additionally constructed a population-specific iodine biokinetic model, hoping to formulate simplified and consistent radiation precautions for GD patients after the 131 I therapy. In view of high interpatient variability in 131 I biokinetics observed in our patient population, basing precautions on a mean or median result would result in an unacceptably high probability of a nearby individual exceeding the regulatory dose limit. Basing precautions on the maximum value may result in unnecessary restrictions to clinical practice and to the behavior of patients and members of their family, however, basing Table 5. Maximum Permissible Times (Hours) to Use Public Transportation After 131 I Therapy Administered Activity, MBq Days After Administration a a The day of 131 I administration. precautions on the upper 95th percentile of actual measurements would provide an upper estimate and represent reasonable worst case (35). Similar strategies have been used previously for calculating nearby individuals radiation doses and formulating radiation precautions for patients receiving 131 I therapy (3, 18). On the basis of the fitted iodine biokinetic model and current regulatory limits, lookup tables were provided for offering radiation safety precautions for GD patients in the study. O Doherty et al (3) have also calculated cumulative exposure doses and developed radiation precautions for hyperthyroid patients treated by 131 I. Such data have been adapted and recommended by the International Commission on Radiological Protection (10) and the International Atomic Energy Agency (12, 14) for radiation precautions in 131 I therapy of hyperthyroidism. Certain differences existed in the calculation of cumulative doses and development of radiation precautions between the study by O Doherty et al and ours. First, even ignoring the effects of attenuation and scatter by the patient s body, the IDRs at1minthestudy by O Doherty et al should have been lower than the unshielding point source value for 131 Iat 1 m, that is, Sv h 1 MBq 1. In our study, the measured IDRs at 1 m ranged from to Sv h 1 MBq 1 (mean Sv h 1 MBq 1 ). This finding was verified by the study by Culver and Dworkin (2) in which the maximum value of IDRs measured within 20 minutes after 131 I administration on 40 hyperthyroid patients was Sv h 1 MBq 1. The results of Culver and Dworkin and ours were also comparable with a study of patients undergoing radioimmunotherapies with 131 I- labeled monoclonal antibodies for non-hodgkin s lymphoma in which the observed IDRs ranged from to Sv h 1 MBq 1 (mean Sv h 1 MBq 1 ) (16). Nevertheless, the mean IDR at 1 m was as high as

7 2940 Liu et al Radiation Safety in 131 I Therapy of Graves Disease J Clin Endocrinol Metab, August 2015, 100(8): Sv h 1 MBq 1 in the study by O Doherty et al (3). Second, the mean value of 131 I clearance half-life (5 d) derived from the patient population was extracted to develop radiation precautions in the study by O Doherty et al. By comparison, the upper 95th percentile of actual assessments was used in our study. Our study had limitations. First, this was a singlecenter experience. Second, the disease-specific thyroid iodine biokinetics has been reported in different forms of hyperthyroidism. In 131 I therapy of other forms of hyperthyroidism, ie, toxic nodular goiter, utilities of the formulated precautions in our study require further study. Third, actual measurements of doses to exposed individuals are necessary to determine the reliability of our precautions. Conclusion The use of actual biokinetic measurements may remove the effect of variability errors associated with general default assumptions about the 131 I biokinetics in GD patients. The marked variability in 131 I biokinetics among GD patients reinforces the need for patient-specific iodine biokinetic measurements for radiation safety precautions. Acknowledgments Address all correspondence and requests for reprints to: Anren Kuang, MD, Department of Nuclear Medicine, West China Hospital, Sichuan University, No 37 Guoxue Alley, Chengdu, China. kuanganren@263.net. This work was supported by National Natural Science Fund of China Grants and Disclosure Summary: The authors have nothing to disclose. References 1. Ross DS. Radioiodine therapy for hyperthyroidism. N Engl J Med. 2011;364(6): Culver CM, Dworkin HJ. Radiation safety considerations for postiodine-131 hyperthyroid therapy. J Nucl Med. 1991;32(1): O Doherty MJ, Kettle AG, Eustance CN, Mountford PJ, Coakley AJ. 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