The influence of saliva flow stimulation on the absorbed radiation dose to the salivary glands during radioiodine therapy of thyroid cancer using 124I PET(/CT) imaging

Purpose

A serious side effect of high-activity radioiodine therapy in the treatment of differentiated thyroid cancer is radiogenic salivary gland damage. This damage may be diminished by lemon-juice-induced saliva flow immediately after ¹³¹I administration. The aim of this study was to assess the effect of chewing lemon slices on the absorbed (radiation) doses to the salivary glands.

Methods

Ten patients received (pretherapy) ¹²⁴I PET(/CT) dosimetry before their first radioiodine therapy. The patients underwent a series of six PET scans at 0.5, 1, 2, 4, 48 and ≥96 h and one PET/CT scan at 24 h after administration of 27 MBq ¹²⁴I. Blood samples were also collected at about 2, 4, 24, 48, and 96 h. Contrary to the standard radioiodine therapy protocol, the patients were not stimulated with lemon juice. Specifically, the patients chewed no lemon slices during the pretherapy procedure and neither ate food nor drank fluids until after completion of the last PET scan on the first day. Organ absorbed doses per administered ¹³¹I activity (ODpAs) as well as gland and blood uptake curves were determined and compared with published data from a control patient group, i.e. stimulated per the standard radioiodine therapy protocol. The calculations for both groups used the same methodology.

Results

A within-group comparison showed that the mean ODpA for the submandibular glands was not significantly different from that for the parotid glands. An intergroup comparison showed that the mean ODpA in the nonstimulation group averaged over both gland types was reduced by 28% compared to the mean ODpA in the stimulation group (p=0.01). Within each gland type, the mean ODpA reductions in the nonstimulation group were statistically significant for the parotid glands (p=0.03) but not for the submandibular glands (p=0.23). The observed ODpAs were higher in the stimulation group because of increased initial gland uptake rather than group differences in blood kinetics.

Conclusion

The ¹²⁴I PET(/CT) salivary gland dosimetry indicated that lemon juice stimulation shortly after ¹³¹I administration in radioiodine therapy increases the absorbed doses to the salivary glands.     

Optimized 124I PET dosimetry protocol for radioiodine therapy of differentiated thyroid cancer.

Iodine kinetics and lesion dose per administered 131I activity (LDpA) of differentiated thyroid cancer metastases were determined using 124I PET. These data were analyzed to derive an optimized dosimetry protocol. METHODS: We evaluated the time-activity-concentration curves of 37 lesions in 17 patients who had undergone thyroidectomies. LDpA determination involved 124I PET images acquired at 4, 24, 48, 72, and 96 h after intake of a capsule containing 20-40 MBq of 124I. A combination of a linear and a monoexponential or a monoexponential function only parameterized the time-activity-concentration curves. The LDpAs, calculated using data from all 5 PET time points, served as reference. The lesions were classified into 3 groups, according to potential for cure with 131I therapy: low (< or =5 Gy GBq(-1); n = 14), medium (between 5 and 10 Gy GBq(-1); n = 9), or high LDpAs (>10 Gy GBq(-1); n = 14). Using the reference approach, the differences in the empiric kinetic parameters within the LDpA groups were evaluated. The reference LDpAs were compared with those derived from only 2, 3, or 4 PET data points and from 1 adapted 2-point approach. Lin's concordance correlation coefficient (rho c) and the mean absolute percentage deviation in LDpAs were used to assess agreement between simplified and reference approaches. RESULTS: The effective 124I half-life, linear activity-concentration rate (alpha), and 24-h activity concentration (CpA) (the latter 2 per administered 124I activity) differed significantly among the LDpA groups (P < 0.05). LDpAs correlated with 24-h CpAs (r = 0.94, P < 0.001). Using the 4-, 24-, and 96-h measurements, a rho c value of greater than or equal to 0.90 was found, and the mean absolute percentage deviation was less than or equal to 16%. Similar statistical values were obtained for the adapted approach, which was based on 24- and 96-h PET data points only. CONCLUSION: Lesion classification into LDpA groups was feasible using a single PET scan at approximately 24 h. Because of the highly variable kinetics, 1 additional measurement at approximately 96 h was needed to obtain a sufficiently reliable LDpA estimate. The adapted 24-96-h approach appears to be the optimal 124I protocol and is a reliable simplification of the 5-point protocol.     

Iodine-124 PET dosimetry in differentiated thyroid cancer: recovery coefficient in 2D and 3D modes for PET(/CT) systems

Purpose This study evaluated the absolute quantification of iodine-124 (¹²⁴I) activity concentration with respect to the use of this isotope for dosimetry before therapies with ¹³¹I or ¹³¹I-labeled radiotherapeuticals. The recovery coefficients of positron emission tomography(/computed tomography) PET(/CT) systems using ¹²⁴I were determined using phantoms and then validated under typical conditions observed in differentiated thyroid cancer (DTC) patients. Methods Transversal spatial resolution and recovery measurements with ¹²⁴I and with fluorine-18 (¹⁸F) as the reference were performed using isotope-containing line sources embedded in water and six isotope-containing spheres 9.7 to 37.0 mm in diameter placed in water-containing body and cylinder phantoms. The cylinder phantom spheres were filled with ¹⁸F only. Measurements in two-dimensional (2D) and three-dimensional (3D) modes were performed using both stand-alone PET (EXACT HR⁺) and combined PET/CT (BIOGRAPH EMOTION DUO) systems. Recovery comparison measurements were additionally performed on a GE ADVANCE PET system using the cylinder phantom. The recovery coefficients were directly determined using the activity concentration of circular regions of interest divided by the prepared activity concentration determined by the dose calibrator. The recovery correction method was validated using three consecutive scans of the body phantom under our ¹²⁴I PET(/CT) protocol for DTC patients. Results Compared with that of ¹⁸F, transversal spatial resolution of ¹²⁴I was slightly, but statistically significantly degraded (7.4 mm vs. 8.3 mm, P<0.002). Using the body phantom, recovery was lower for ¹²⁴I than for ¹⁸F in both 2D and 3D modes. The ¹²⁴I recovery coefficient of the largest sphere was significantly higher in 2D than in 3D mode (81% vs. 75%, P=0.03). Remarkably, the ¹⁸F recovery coefficient for the largest sphere significantly deviated from unity (range of 87%–93%, P<0.004) for all scanners but the GE ADVANCE. The maximum range of inaccuracy of the measured ¹²⁴I activity concentration under in vivo conditions after applying partial volume correction was ±10% for spheres ≥12.6 mm in diameter. Conclusions Recovery correction is mandatory for ¹²⁴I PET quantification, even for large structures. To ensure accurate dosimetry, thorough absolute recovery measurements must be individually established for the particular PET scanner and radionuclide to be used.     

Three-dimensional radiobiological dosimetry (3D-RD) with 124I PET for 131I therapy of thyroid cancer

Radioiodine therapy of thyroid cancer was the first and remains among the most successful radiopharmaceutical (RPT) treatments of cancer although its clinical use is based on imprecise dosimetry. The positron emitting radioiodine, (124)I, in combination with positron emission tomography (PET)/CT has made it possible to measure the spatial distribution of radioiodine in tumors and normal organs at high resolution and sensitivity. The CT component of PET/CT has made it simpler to match the activity distribution to the corresponding anatomy. These developments have facilitated patient-specific dosimetry (PSD), utilizing software packages such as three-dimensional radiobiological dosimetry (3D-RD), which can account for individual patient differences in pharmacokinetics and anatomy. We highlight specific examples of such calculations and discuss the potential impact of (124)I PET/CT on thyroid cancer therapy.     

Prediction of absorbed dose to normal organs in thyroid cancer patients treated with 131I by use of 124I PET and 3-dimensional internal dosimetry software.

The objective of this work was to determine normal organ (131)I dosimetry in patients undergoing radioiodide therapy for thyroid cancer by use of serial scanning with (124)I PET. METHODS: A total of 26 patients who had papillary and follicular metastatic thyroid cancer and who were already enrolled in a Memorial Sloan-Kettering Cancer Center (131)I thyroid cancer protocol were selected for this study. Imaging before (131)I therapy consisted of multiple, whole-body (124)I PET studies over a period of 2-8 d, an (18)F-FDG PET scan and, for some, a diagnostic CT scan. With a set of in-house-developed software tools (3-dimensional internal dosimetry [3D-ID] and Multiple Image Analysis Utility [MIAU]), the following procedures were performed: all PET emission and transmission and CT image sets were aligned; half-life-corrected tomographic images of (131)I activity were integrated voxel by voxel to produce cumulated (131)I activity images; and the latter images were, in turn, convolved with a (131)I electron-photon point kernel to produce images of (131)I dose distribution. Cumulated activity values and calculated residence times obtained from our patient-specific dosimetry software (3D-ID) were used as inputs to OLINDA, and volume difference-adjusted comparisons were made between the mean dose estimates. RESULTS: With 3D-ID, dose volume histograms and mean doses were calculated for 14 organs, and results were expressed in Gy/GBq. The highest mean dose, 0.26 Gy/GBq, was seen in the right submandibular gland, whereas the lowest mean dose, 0.029 Gy/GBq, was seen in the brain. CONCLUSION: This is the first comprehensive study of normal organ dosimetry in patients by use of a quantitative tomographic imaging modality.     

124I PET/CT in the pretherapeutic staging of differentiated thyroid carcinoma: comparison with posttherapy 131I SPECT/CT

Purpose

To compare pretherapy ¹²⁴I PET/CT and posttherapy ¹³¹I SPECT/CT in the identification of pathological lesions and the staging of patients with differentiated thyroid carcinoma.

Methods

¹²⁴I SPECT with low-dose CT in addition to a standard whole-body scan was performed 5 days following ¹³¹I therapy with the administration of 1,110–7,728 MBq. Pretherapy ¹²⁴I PET/CT was done 24 h and 96 h after oral ingestion of 20–28 MBq, including a noncontrast high-dose CT scan. Scans were evaluated by two independent experienced nuclear physicians. In addition to the total number of lesions found, patient-based analyses and lesion-based analyses were performed to ascertain the discrepancies between the findings of the two scanning techniques, as well as to evaluate the clinical impact of the findings.

Results

A group of 20 consecutive patients were analysed. In the lesion-based analysis, a total of 62 foci were found with all modalities together. Of these, ¹²⁴I PET/CT found 57 (92 %), ¹³¹I SPECT/CT 50 (81 %) and planar imaging 39 (63 %). In the patient-based analysis, in 50 % of patients complete concordance between the findings of ¹²⁴I PET and ¹³¹I SPECT was seen, in 5 % complete discordance and in the remaining 45 % partial discordance, i.e. a focus or some foci seen with both modalities but another or others seen more or less with one or other modality. In 5 of the 20 patients (25 %), tumour stage was changed according to the findings of one of the modalities. In 60 % of these patients this was only with the findings of ¹²⁴I PET/CT.

Conclusion

This study showed that ¹²⁴I PET/CT is preferred over ¹³¹I imaging for staging differentiated thyroid carcinoma.     

Pre-therapeutic blood dosimetry in patients with differentiated thyroid carcinoma using 124-iodine: predicted blood doses correlate with changes in blood cell counts after radioiodine therapy and depend on modes of TSH stimulation and number of preceding radioiodine therapies

Objective

Pre-therapeutic blood dosimetry prior to a high-dose radioiodine therapy (RAIT) is recommended and a blood dose of 2?Gy is considered to be safe. In this study, changes in the blood cell count after radioiodine therapy of high risk differentiated thyroid carcinoma (DTC) were analyzed and compared with the results of the pre-therapeutic blood dosimetry using ¹²⁴I. Moreover, the influence of different modes of TSH stimulation and the number of preceding radioiodine therapies on the blood dose were assessed.

Methods

198 patients with locally advanced or metastasized DTC received a pre-therapeutic blood dosimetry using ¹²⁴I. To analyze the influence of the modes of TSH stimulation and the number of preceding RAITs on blood dose subgroups were built as follows: patients with endogenous TSH stimulation versus patients with exogenous TSH stimulation and patients with no preceding RAIT versus patients with at least one preceding RAIT. In 124/198 patients subsequent RAIT was performed. In 73/124 patients, hemograms were performed from day 2 to 12?month after RAIT.

Results

There was no high-grade bone marrow toxicity (i.e. ??grade 3) in patients receiving less than 2?Gy blood dose??independent of the therapeutic history. Within the first month after radioiodine therapy, there was an overall decrease in the white blood cell and platelet counts. The erythrocyte count was essentially stable. There was a correlation between cell count decrease and predicted blood doses (Spearman??s correlation coefficient >?0.6 each) for the white cell line and the platelets. With regard to the subgroups, the blood dose per administered ¹³¹I activity (BDpA) was significantly higher in patients with endogenous TSH stimulation (median 0.08?Gy/GBq) than in patients with exogenous TSH stimulation (0.06?Gy/GBq) and in patients with no previous RAIT (0.08?Gy/GBq) compared to patients who had previously undergone at least one RAIT (0.07?Gy/GBq).

Conclusions

The range of BDpA among DTC patients is rather wide. Our results suggest that lower blood doses can be expected when using exogenous TSH stimulation and blood doses are generally higher at first RAIT compared to subsequent RAITs. Thus, we advise to make blood dosimetry standard praxis prior to a high-activity RAIT.     

Disseminated iodine-avid lung metastases in differentiated thyroid cancer: a challenge to 124I PET

Aim This study assessed the ability of visual and quantitative 124-iodine positron emission tomography (¹²⁴I PET) data to detect disseminated iodine-avid lung metastases (DILM) of differentiated thyroid cancer (DTC). Materials and methods Using “post-therapy” 131-iodine (¹³¹I) whole-body scintigraphy (TxWBS) and thoracic computed tomography (CT), we retrospectively divided 70 consecutive DTC patients undergoing ¹²⁴I PET dosimetry ∼1 week before ¹³¹I therapy into subgroups positive (n = 7) or negative (n = 63) for DILM, defined as lung metastases visible on TxWBS but not thoracic CT. To determine whether ¹²⁴I PET data could distinguish patients with versus without DILM, we compared these data with the TxWBS findings. The ¹²⁴I PET data were acquired via whole-body PET scans ∼24 h after oral administration of ¹²⁴I, 24 ± 2 MBq. Quantitative data comprised absolute lung ¹²⁴I activity concentrations and lung-to-background (L/B) ¹²⁴I uptake ratios. Results Only 1/7 DILM-positive patients had visible disseminated lung uptake. Absolute ¹²⁴I lung uptake activities overlapped considerably between both groups and did not differ significantly (P = 0.150). Mean L/B ratios, however, differed significantly between the DILM-positive and negative groups (P < 0.001). Nevertheless, L/B ratios overlapped between the groups (0.62–1.37 versus 0.13–0.69). Conclusion Quantitative analysis of ¹²⁴I PET data using the L/B ratio is a promising tool to detect patients suspicious for DILM. However, L/B ratios overlapped between the groups to an extent that an unequivocal diagnosis based solely on this criterion was impossible in some patients. In those cases, additional diagnostic tests are necessary for diagnosis.     

中低危分化型甲状腺癌术后131I清甲治疗后血清甲状腺球蛋白的变化

目的 探讨患中低危DTC初次131I治疗后6个月复查131I全身显像(WBS)示阴性、刺激性Tg阳性(≥10.00 μg/L)患者Tg的转归情况.方法 回顾性分析56例按美国甲状腺学会(ATA)指南诊断其复发危险分层为中低危的DTC患者[男20例,女36例,平均年龄43.11(21～70)岁],患者均经甲状腺全切除术+131I清除残余甲状腺组织+甲状腺激素抑制治疗,均于131I治疗后6个月停用甲状腺激素,复查131I WBS均为阴性.此时刺激性Tg≥10.00 μg/L即为刺激性Tg阳性.56例中,刺激性Tg阳性组19例,阴性组37例,追踪2组131I治疗后1年及2.5年抑制性Tg变化,同时监测颈部超声表现等变化.采用SPSS 17.0软件对数据进行两样本t检验和x2检验.结果 刺激性Tg阳性组131I治疗后6个月血清刺激性Tg明显高于阴性组,分别为(24.27±4.10)与(2.73±3.01)μg/L(t=7.191,P＜0.05);阳性组中68.4％ (13/19)的患者血清抑制性Tg水平随时间呈逐渐下降趋势,131I治疗后2.5年时为(0.53±0.15) μg/L,比治疗后1年时的(1.38±0.50) μg/L低;阳性组131I治疗后1年时抑制性Tg仍高于阴性组[(2.21±0.55)与(0.48±0.10) μg/L;t=3.102,P＜0.05],至2.5年时,2组差异无统计学意义[(1.44±0.52)与(0.38±0.07) μg,/L;t=2.001,P＞O.05].2组各有l例患者治疗后2年时随访颈部超声发现肿大淋巴结(抑制性Tg分别为1.4和0.1 μg/L),经术后病理证实为淋巴结转移性甲状腺癌.结论 131I治疗后6个月刺激性Tg阳性的中低危DTC患者血清Tg水平随时间呈下降趋势,此时停用甲状腺激素行131I WBS的意义及经验性131I治疗的价值有待进一步探讨.     

rhTSH stimulation before radioiodine therapy in thyroid cancer reduces the effective half-life of (131)I.

Recombinant human thyroid-stimulating hormone (rhTSH) is effectively used for exogenous thyroid-stimulating hormone (TSH) stimulation before diagnostic (131)I scintigraphy. It is not yet widely used for preparation of patients receiving a therapeutic amount of radioiodine. METHODS: The results of 64 consecutive therapeutic applications of rhTSH with regard to clinical tolerance and side effects were evaluated in comparison with 163 radioiodine therapies (RITs) done on patients with hypothyroidism after thyroxine withdrawal during the same period. All therapies-applying 1.1-10 GBq of (131)I-used a standardized protocol of patient preparation and activity application. RITs were followed by daily whole-body uptake measurements for 2-6 d, and a biexponential curve fit was used to obtain a short initial and afterward a long effective half-life of (131)I. Patients after rhTSH were evaluated as a whole group (group A, n = 64) and as a subset of that group with normal thyroglobulin (hTG) levels (group D, n = 18). Patients after endogenous TSH stimulation were evaluated as a whole group (group B, n = 163), as a subset of that group excluding all ablative RITs (group C, n = 113), and as a subset of that subset with normal hTG levels (group E, n = 87). RESULTS: rhTSH-stimulated patients showed significantly higher TSH values than did endogenously stimulated patients (P < 0.001). Furthermore, the effective half-life of (131)I was significantly prolonged after endogenous stimulation (e.g., 0.43 d for group A vs. 0. 54 d for group B, P < 0.001). All rhTSH applications were tolerated well and without serious side effects. The only side effects were 2 cases of nausea and headache. CONCLUSION: The use of rhTSH for stimulation of TSH before RIT is safe but also significantly reduces the effective half-life of (131)I. This is mainly due to a reduced renal iodine clearance in the hypothyroid state, but the bioavailability of radioiodine may be slightly overestimated because of larger amounts of intestinal (131)I after endogenous TSH stimulation.     

Diagnosis and dosimetry in differentiated thyroid carcinoma using <Superscript>124</Superscript>I PET: comparison of PET/MRI vs PET/CT of the neck

Purpose  

This study compares intrinsically coregistered ¹²⁴I positron emission tomography (PET) and CT (PET/CT) and software coregistered ¹²⁴I PET and MRI (PET/MRI) images for the diagnosis and dosimetry of thyroid remnant tissues and lymph node metastases in patients with differentiated thyroid carcinoma (DTC).     

The management of differentiated thyroid cancer using 123I for imaging to assess the need for 131I therapy

BACKGROUND: Follow-up of 131I whole-body scanning after 131I ablation is associated with potential stunning. Previous studies have suggested that, for scanning, 123I is more sensitive than 131I in identifying thyroid tissue, but its specificity when positive is less certain. AIM: The use of 123I as an imaging agent in place of serial 131I imaging has been evaluated in the surveillance and treatment of differentiated thyroid carcinoma. RESULTS: A total of 186 studies in 136 patients with differentiated thyroid carcinoma were evaluated after total or near total thyroidectomy followed by 131I ablation. In 125 studies 123I scanning was negative and no 131I therapy was given; four patients were positive on 123I scanning but for other reasons no 131I therapy was given. In 48/49 patients a positive 123I scan was followed by positive 131I therapeutic uptake. Only one patient failed to show positive uptake of I when first treated and she subsequently demonstrated uptake on a second therapy. CONCLUSION: High-dose 123I imaging is the correct predictor of the 131I post-therapy scan findings in most cases, at an administered activity that avoids stunning. As a diagnostic agent it is preferable to 131I in differentiated thyroid carcinoma.     

Quantification of absorbed doses to urine bladder depending on drinking water during radioiodine therapy to thyroid cancer patients: a clinical study using MIRDOSE3

The object of the study was to quantify the absorbed doses to urinary bladder using MIRDOSE3 (medical internal radiation dose package program) depending on drinking water after giving radioiodine dose to thyroid cancer patients. Twenty-nine female thyroid cancer patients (aged 40-60 years, mean 50 years) were selected. The therapeutic doses ranged from 3700 to 7400 MBq of 131I. The radioiodine uptake was measured at 1 cm distance from three organs (previously marked), the thyroid, thigh and stomach, by using a calibrated Eberline ESP-2 GM counter, with a special arrangement of each patient. Urine samples were collected every 12 h for first 72 h, and then every 24 h for the next 96 h. The individual biological half-life of excreted urine was calculated using individual effective half-life. Absorbed doses were calculated for an adult female phantom using the dynamic bladder model of MIRDOSE3 program in two phases: firstly, for different voiding intervals; and secondly, depending on individual drinking water. An average of 85% of the total dose passed through the urinary tract within the first 72 h, with a biological half-life of 28.5+/-0.747 h, and 9% for the next 96 h with a biological half life of 118.43+/-0.645 h. The voiding interval shows great impact on total absorbed dose to bladder and water supplementation needs to be intensified to reduce absorbed doses to bladder wall for the first 3 days.     

Radiation dosimetry and first therapy results with a 124I/131I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy

Introduction

Since the prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) several PSMA-targeting molecules are under development to detect and treat metastatic castration resistant prostate cancer (mCRPC). We investigated the tissue kinetics of a small molecule inhibitor of PSMA ((S)-2-(3-((S)-1-carboxy-5-(3-(4-[¹²⁴I]iodophenyl)ureido)pentyl)ureido)pentanedioicacid; MIP-1095) using PET/CT to estimate radiation dosimetry for the potential therapeutic use of ¹³¹I-MIP-1095 in men with mCRPC. We also report preliminary safety and efficacy of the first 28 consecutive patients treated under a compassionate-use protocol with a single cycle of ¹³¹I-MIP-1095.

Methods

Sixteen patients with known prostate cancer underwent PET/CT imaging after i.v. administration of ¹²⁴I-MIP-1095 (mean activity: 67.4 MBq). Each patient was scanned using PET/CT up to five times at 1, 4, 24, 48 and 72 h post injection. Volumes of interest were defined for tumor lesions and normal organs at each time point followed by dose calculations using the OLINDA/EXM software. Twenty-eight men with mCRPC were treated with a single cycle of ¹³¹I-MIP-1095 (mean activity: 4.8 GBq, range 2 to 7.2 GBq) and followed for safety and efficacy. Baseline and follow up examinations included a complete blood count, liver and kidney function tests, and measurement of serum PSA.

Results

I-124-MIP-1095 PET/CT images showed excellent tumor uptake and moderate uptake in liver, proximal intestine and within a few hours post-injection also in the kidneys. High uptake values were observed only in salivary and lacrimal glands. Dosimetry estimates for I-131-MIP-1095 revealed that the highest absorbed doses were delivered to the salivary glands (3.8 mSv/MBq, liver (1.7 mSv/MBq) and kidneys (1.4 mSv/MBq). The absorbed dose calculated for the red marrow was 0.37 mSv/MBq. PSA values decreased by >50 % in 60.7 % of the men treated. Of men with bone pain, 84.6 % showed complete or moderate reduction in pain. Hematological toxicities were mild. Of men treated, 25 % had a transient slight to moderate dry mouth. No adverse effects on renal function were observed.

Conclusion

Based on the biodistribution and dose calculations of the PSMA-targeted small molecule ¹²⁴I-MIP-1095 therapy with the authentic analog ¹³¹I-MIP-1095 enables a targeted tumor therapy with unprecedented doses delivered to the tumor lesions. Involved lymph node and bone metastases were exposed to estimated absorbed doses upwards of 300 Gy.     

Radiation dose to the testes after 131I therapy for ablation of postsurgical thyroid remnants in patients with differentiated thyroid cancer.

Radioiodine-131 is used in differentiated thyroid cancer (DTC) for ablation of postsurgical thyroid remnants and destruction of metastases. The question may be raised of whether 131I treatment of DTC in male patients may give an irradiation dose to the testes that could impair fertility. Few data in the literature concern the dose absorbed by the testes after 1311 therapy for DTC. Because 131I kinetics may be altered by the hypothyroid condition commonly present at the time of treatment and by the radioiodinated iodoproteins released by the damaged thyroid tissue, the dose values reported in the International Commission on Radiological Protection (ICRP) tables for euthyroid men may not be appropriate. To clarify this problem, three male subjects undergoing 131I therapy for ablation of thyroid remnants shortly after thyroidectomy for DTC were studied. METHODS: The mean administered activity was 1256 MBq, and the duration of the study was 2 wk. The gamma dose was measured by thermoluminescent dosimeters (TLDs) applied to the lower poles of the testes. Correction factors were calculated for the distance of the TLD from the center of the testes and for attenuation by the testes of the gamma rays reaching the TLD. After correction, the gamma dose to the testes ranged from 21 to 29 mGy. The gamma dose calculated by the Medical Internal Radiation Dose (MIRD) method from blood and urine samples was similar (18-20 mGy) to that measured by TLDs. The beta dose was estimated by the MIRD method from blood activity and testicular volume and ranged between 14 and 31 mGy. Results: The total (beta and gamma) doses to testes were 30, 33 and 43 microGy/MBq in the three subjects. CONCLUSION: These values are close to those derived from the ICRP tables (26-37 microGy/MBq 131I) for euthyroid subjects. The present data indicate that significant irradiation is delivered to the testes after the administration of the 131I ablative dose to thyroidectomized patients. The relevance of the radiation absorbed by testes on fertility remains to be established.     

Bone marrow dosimetry and safety of high 131I activities given after recombinant human thyroid-stimulating hormone to treat metastatic differentiated thyroid cancer.

Recombinant human thyroid-stimulating hormone (rhTSH) recently was introduced as a radioiodine administration adjunct that avoids levothyroxine (LT-4) withdrawal and resultant hypothyroidism. The pharmacokinetics of 131I after rhTSH administration are known to differ from those after LT-4 withdrawal but are largely nondelineated in the radioiodine therapy setting. We therefore sought to calculate the red marrow absorbed dose of high therapeutic activities of 131I given after rhTSH administration to patients with metastatic or inoperable locally recurrent differentiated thyroid cancer. We also sought to evaluate the clinical and laboratory effects of this therapy on the bone marrow. METHODS: Fourteen consecutive patients received in total 17 131I treatments (7.4 GBq). Blood and urine samples were obtained at fixed intervals, and their activities were measured in a well counter. Based on blood activity, renal clearance of the activity, and residence times in red marrow and the remainder of the body, the red marrow absorbed dose was calculated using the MIRD schema. Additionally, we monitored for potential hematologic toxicity and compared platelet counts before and 3 mo after treatment. RESULTS: The mean +/- SD absorbed dose per unit of administered (131)I in the red marrow was 0.16 +/- 0.07 mGy/MBq. The corresponding total red marrow absorbed dose was 1.15 +/- 0.52 Gy (range, 0.28-1.91 Gy). In none of the patients was hematologic toxicity observed. The mean +/- SD platelet count (n = 13 treatments) was 243 +/- 62 x 10(9)/L before treatment and 233 +/- 87 x 10(9)/L 3 mo later, a slight and statistically insignificant decrease. After rhTSH-aided administration of high activities of 131I, the bone marrow absorbed dose remained under 2 Gy, the level long considered the safety threshold for all radioiodine therapy. CONCLUSION: Our specific findings imply that when clinically warranted, rhTSH should allow an increase in the therapeutic radioiodine activity. Such an increase might improve efficacy while preserving safety and tolerability; this possibility should be assessed in further studies.