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131 I-metaiodobenzylguanidine ( 131 I-MIBG) is a theranostic agent useful for treatment of neuroendocrine malignancies. In this case, a child with a Curie score of 21 was administered 17.871 GBq (483 mCi) of 131 I-MIBG. The elimination half-life progressively increased from 23 h to 77 h during the 11 d that the patient was hospitalized for radiation isolation. Six weeks after the posttherapy scan, a survey with an ion-chamber device yielded readings of 0.3 μSv/h (0.03 mR/h) on contact with spinal regions that had shown increased uptake on the scan. A planar image obtained using the 131 I setting and a high-energy collimator did not demonstrate any focal uptake. 123 I-MIBG was administered, and the 24-h scan was of diagnostic quality, without degradation from the remaining 131 I-MIBG. Additional study is needed on whether the Curie score affects elimination of 131 I-MIBG and on whether the period of hospitalized radiation isolation needs to be extended., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

This paper presents a fast and automatic flow-based method to extract 131 I from biological samples and hospital waste, previous to liquid scintillation detection. 131 I is a radionuclide extensively used in Nuclear Medicine due to their beta and gamma disintegrations, whereby hospitals have to manage the associated waste generation. The automatic developed system is based on Lab-On-Valve (LOV) flow-technique exploiting Cl-resin (135 mg per extraction). This methodology allows performing sample extractions and measurements on the same day, since the extraction frequency takes 1.4-4 h -1 , depending on the analysed sample volume, plus up to 2 h of measurement for each vial. 131 I is retained as iodine ion and eluted with sodium sulphide 0.2 mol L -1 . The maximum sample volume that can be preconcentrated is 20 mL, reaching an extraction efficiency of 85 ± 5%. The minimum detectable activity (MDA) is 0.05 Bq, showing a precision of 7% RSD (n = 5). Both, biological samples (urine and saliva) and hospital waste samples can be satisfactorily analysed by the proposed system, obtaining recoveries between 90 and 110%. The developed method is then suitable to implement in hospitals, improving the surveillance of the 131 I environmental release., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Objectives: Glomerular hyperfiltration has been considered to be a contributing factor to the development of diabetic kidney disease (DKD). To address this issue, we analyzed GFR follow-up data on participants with type 1 diabetes undergoing 125 I-iothalamate clearance on entry into the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications study., Design, Setting, Participants, & Measurements: This was a cohort study of DCCT participants with type 1 diabetes who underwent an 125 I-iothalamate clearance (iGFR) at DCCT baseline. Presence of hyperfiltration was defined as iGFR levels ≥140 ml/min per 1.73 m 2 , with secondary thresholds of 130 or 150 ml/min per 1.73 m 2 . Cox proportional hazards models assessed the association between the baseline hyperfiltration status and the subsequent risk of reaching an eGFR <60 ml/min per 1.73 m 2 ., Results: Of the 446 participants, 106 (24%) had hyperfiltration (iGFR levels ≥140 ml/min per 1.73 m 2 ) at baseline. Over a median follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73 m 2 . The cumulative incidence of eGFR <60 ml/min per 1.73 m 2 at 28 years of follow-up was 11.0% among participants with hyperfiltration at baseline, compared with 12.8% among participants with baseline GFR <140 ml/min per 1.73 m 2 . Hyperfiltration was not significantly associated with subsequent risk of developing an eGFR <60 ml/min per 1.73 m 2 in an unadjusted Cox proportional hazards model (hazard ratio, 0.83; 95% confidence interval, 0.43 to 1.62) nor in an adjusted model (hazard ratio, 0.77; 95% confidence interval, 0.38 to 1.54). Application of alternate thresholds to define hyperfiltration (130 or 150 ml/min per 1.73 m 2 ) showed similar findings., Conclusions: Early hyperfiltration in patients with type 1 diabetes was not associated with a higher long-term risk of decreased GFR. Although glomerular hypertension may be a mechanism of kidney injury in DKD, higher total GFR does not appear to be a risk factor for advanced DKD., (Copyright © 2019 by the American Society of Nephrology.)

Sufficient thyroid iodine uptake is needed to ensure effective radioactive iodine (RAI) treatment, which is mediated by the sodium-iodide symporter (NIS). Activation of AMP-activated-protein-kinase (AMPK), leads to decreased NIS expression and thyroid iodine uptake in in vitro and animal models. Clinically relevant conditions that lead to AMPK activation include metformin use and hypocaloric conditions. Here, we aim to assess the effects of metformin and hypocaloric diet on thyroid iodine uptake in healthy volunteers. Healthy male volunteers were included and randomized. Group 1 (n = 8) received metformin, group 2 (n = 7) followed a hypocaloric diet (1500 kcal/day), superposed on a moderate iodine restriction diet; Baseline measurements included thyroid iodine-123 (I-123) uptake and TSH, fT4, T3 and rT3 levels. After two weeks, thyroid function and I-123 uptake measurements were repeated. Baseline characteristics were similar between groups. Levels of TSH and fT4 were similar after each intervention. T3 decreased after hypocaloric diet and metformin (-0.2 ± 0.19 nmol/L, p = 0.0327; respectively -0.13 ± 0.13 nmol/L, p = 0.0282), resulting in decreased T3/rT3 ratios. There was no significant difference in thyroid I-123 uptake after each intervention. In conclusion, metformin treatment and hypocaloric diet resulted in a significant decrease in T3 levels and T3/rT3 ratios in healthy volunteers, without significant effects on thyroid iodine uptake. We found no indications that metformin or hypocaloric diet will have clinically relevant effects on RAI uptake.

Purpose: To investigate the internal exposure of nuclear medicine practitioners in South Korea., Methods: This study selected nuclear medicine practitioners among domestic hospitals and quantitatively measured their degree of internal exposure to radioisotopes, and conducted a dose assessment based on the results. For the dose assessment, 35 nuclear medicine practitioners at seven large hospitals were selected as the measurement subjects, and the measurements were obtained using the thyroid count, total body count, and a urine sample analysis. The internal exposure was measured once every two weeks, and measurements were obtained three to 15 times according to the practitioners., Results: As a result of measuring and analyzing the radionuclides with urine samples, one or more detections above the minimum detectable activity (MDA) was identified in 52 (15%) among all 340 cases for 14 of the practitioners (43%). The committed effective doses were evaluated as have a distribution of zero to 5.4 mSv, and were mostly 1 mSv or less. There were four practitioners exceeding 1 mSv based on the whole-body measurements, whose results from a urine sample analysis and thyroid monitoring all showed exposure of 1 mSv or less. All of the practitioners participated directly in the distribution and handling of radioactive sources, and none of the nurses exceeded 1 mSv. Furthermore, it was noteworthy that, among medical assistants who do not directly handle radioisotopes and are mainly involved in the transport of contaminated patients, there was one person who exceeded the whole-body measurement standard of 1 mSv., Conclusions: The committed effective dose of most nuclear medicine practitioners who participated in the survey was lower than 1 mSv. However, because the possibility of overexposure under special circumstances cannot be completely excluded, new strict radiation protection rules on the handling of open-source radioisotopes in hospitals are required for non-handling workers., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Radioiodine therapy could be challenging in chronic renal failure patients requiring hemodialysis. The aim of this study was to establish the effects of hemodialysis on elimination of radioiodine from the body in thyroid carcinoma patients with end-stage chronic renal failure and to determine its effects on environmental radiation dose., Materials and Methods: Three end-stage chronic renal failure patients (four cases) diagnosed with differentiated thyroid carcinoma requiring radioiodine therapy were included in our study. Each patient was given 50-75 mCi (1850-2775 MBq) iodine-131 with 50% dose reduction. Dose rate measurement was performed at the 2nd, 24th, and 48th hour (immediately before and after hemodialysis) after radioiodine administration. The Geiger-Müller probe was held at 1 m distance at the level of the midpoint of the thorax for the dose rate measurement., Results and Conclusion: The effective half-life of iodine-131 for three patients was found to be 44 h. In conclusion, the amount of radioiodine excreted per hemodialysis session was calculated to be 51.25%.

Objective: Serum thyroglobulin (Tg) has been associated with a number of thyroid disorders and has been proposed as an indicator of iodine deficiency in a population. However, few studies have addressed the epidemiology of Tg in a population-based setting or in the context of exposure to radioactive iodine-131 (I-131). Our objective was to evaluate baseline levels of Tg in relation to sociodemographic characteristics, iodine status and thyroid function for individuals exposed to I-131., Design: A population-based cohort assembled in Belarus following the Chornobyl accident provided demographic factors, clinical data and physiological measurements., Participants: Our analytical sample included 10,344 subjects of whom 7890 had no thyroid disease and 2454 had evidence of structural or functional thyroid abnormality., Measurements: Standardized assays were used to measure serum Tg, urinary iodine, TSH and antibodies to Tg and thyroid peroxidase. Ultrasound was used to assess the presence of nodules and estimate thyroid volume., Results: In the fully adjusted model, percent change in Tg was significantly increased among females, smokers and subjects of older age and Tg increased with decreasing urinary iodine concentration, increasing serum TSH and increasing thyroid volume (P-values for trend <0·0001), and presence of thyroid nodules (P < 0·05). We found a complex interaction between region of residence, rural/urban living, presence/absence of thyroid abnormalities and serum Tg (P < 0·0001)., Conclusions: In residents of Belarus, serum Tg is significantly related to presence of thyroid abnormalities as well as indicators of thyroid function and iodine deficiency and, therefore, could be used to characterize the iodine status and thyroid function of individuals in the context of epidemiological study., (© 2012 John Wiley & Sons Ltd.)

Importance: Patients who undergo radiographic studies with contrast receive an enormous bolus of iodine. This can delay subsequent use of radioactive iodine (RAI) therapy because the iodine can compete for uptake. There is a paucity of literature on the minimum interval between contrast administration and RAI therapy., Objective: To better characterize how long it takes for the iodine load from an intravenous contrast bolus to clear from the body., Design, Setting, and Participants: A prospective cohort of 21 adults undergoing intravenous contrast CT studies at a tertiary academic medical center; exclusion criteria included history of thyroid disease or thyroidectomy, history of renal insufficiency, pregnancy, and other contrast administration within 1 year., Intervention: Morning urine samples were taken before the scan for analysis and then every 2 weeks thereafter for 12 weeks. RESULTS The median baseline iodine level was 135 μg/L (range, 29-1680 μg/L), and median peak level was 552 μg/L (range, 62-6172 μg/L). Median time for urinary iodine level to normalize was 43 days, with 75% of subjects returning to baseline within 60 days, and 90% of subjects within 75 days. Baseline iodine level was a significant predictor of postcontrast iodine levels. Age, sex, weight, and estimated glomerular filtration rate were not significant., Conclusions and Relevance: These results may be used for guidance on the timing of RAI use following contrast exposure. The practice at our institution is to wait 2 months and then check a 24-hour urinary iodine level. This alleviates concerns about contrast use in patients with thyroid carcinoma interfering with adjuvant radioiodine therapy.

The aim of this study was to determine the external dose rate of iodine retention as a function of time in the bodies of thyroid cancer patients during their isolation period in the hospital. Urine samples were collected at 6th, 12th, 18th, 24th h and 2nd, 3rd, 4th, 5th d from 83 patients after oral administration of (131)I and counted. The external dose rates were also simultaneously determined at the same time points. Then, it was expressed as retained radioiodine body activity versus dose rate. Effective half life calculated from urine sample measurements was found as 18.4±1.8 h within the first 24 h and 64±2.7 h between 48 and 120 h. According to this results, the external dose rate (<20 µSv h(-1)), which patients could be discharged, was achieved after 48 h for 3700 and 5550 MBq, and after 72 h for 7400 MBq of (131)I treatments.

Radioactive iodide ((131)I-) protection studies have focused primarily on the thyroid gland and disturbances in the hypothalamic-pituitary-thyroid axis. The objective of the current study was to establish (131)I- urinary excretion profiles for saline, and the thyroid protectants, potassium iodide (KI) and ammonium perchlorate over a 75 hour time-course. Rats were administered (131)I- and 3 hours later dosed with either saline, 30 mg/kg of NH(4)ClO(4) or 30 mg/kg of KI. Urinalysis of the first 36 hours of the time-course revealed that NH(4)ClO(4) treated animals excreted significantly more (131)I- compared with KI and saline treatments. A second study followed the same protocol, but thyroxine (T(4)) was administered daily over a 3 day period. During the first 6-12 hour after (131)I- dosing, rats administered NH(4)ClO(4) excreted significantly more (131)I- than the other treatment groups. T(4) treatment resulted in increased retention of radioiodide in the thyroid gland 75 hour after (131)I- administration. We speculate that the T(4) treatment related reduction in serum TSH caused a decrease synthesis and secretion of thyroid hormones resulting in greater residual radioiodide in the thyroid gland. Our findings suggest that ammonium perchlorate treatment accelerates the elimination rate of radioiodide within the first 24 to 36 hours and thus may be more effective at reducing harmful exposure to (131)I- compared to KI treatment for repeated dosing situations. Repeated dosing studies are needed to compare the effectiveness of these treatments to reduce the radioactive iodide burden of the thyroid gland.

Activities of (131)I and (137)Cs excreted in urine from two healthy males during May 1986, when contaminated air masses from Chernobyl arrived on the territory of the Czech Republic, were determined by bioassay. The data were used to estimate the intakes and committed effective doses from these radionuclides. The results for inhalation intakes are of particular interest, in the absence of sufficient contemporary data for airborne activity. They are found to be higher than initial estimates based on air sampling.

Context: Tyrosine kinase inhibitors (TKI) are used for the treatment of various cancers. Case reports and clinical trials have reported abnormal thyroid function tests (TFT) after treatment with sunitinib, imatinib, sorafenib, dasatinib, and nilotinib. An increased requirement for levothyroxine was reported in thyroidectomized patients during TKI treatment., Objective: We hypothesized that abnormal TFT are compatible with inhibition of thyroid hormone (TH) transporters and subsequently reduced pituitary-TH feedback. Monocarboxylate transporter 8 (MCT8) is a TH transmembrane transporter in brain, pituitary, and other organs. MCT8 mutation leads to abnormal TFT in patients and respective mouse models. We tested whether TKI are able to inhibit MCT8-mediated TH uptake into cells., Design: Madin-Darby-canine kidney (MDCK1) cells stably expressing human MCT8 were exposed in vitro to TKI at increasing concentrations, and MCT8-mediated [(125)I]T(3) uptake and efflux were measured. The mode of inhibition was determined., Results: TKI exposure dose-dependently inhibited MCT8-dependent T(3) and T(4) uptake. IC(50) values for sunitinib, imatinib, dasatinib, and bosutinib ranged from 13-38 μm, i.e. similar to the Michaelis-Menten constant K(m) for T(3) and T(4), 4 and 8 μm, respectively. Kinetic experiments revealed a noncompetitive mode of inhibition for all TKI tested., Conclusions: Partial inhibition by TKI of pituitary or hypothalamic TH feedback may increase TSH or increase the levothyroxine requirement of thyroidectomized patients. It is still possible that other mechanisms contribute to TKI-mediated impairments of TFT, e.g. altered metabolism of TH. Bosutinib was not previously reported to alter TFT.

In nuclear medicine, estimating the radioactivity contained in the urine of patients treated with I and discharged to the environment could prevent the exposure of a population to radioactive effluents and the pollution of the aquatic environment with ionizing radiation. This can be a regulatory requirement (as in Spain) or requested by the sewer authority. Seventy-nine differentiated thyroid cancer cases (undergone as inpatients) and 187 hyperthyroidism cases (undergone as outpatients) were treated in our hospital with I throughout the year 2009. In hyperthyroidism treatments, the effective elimination constant was used to calculate the corresponding discharged activity in the urine, giving an activity level always below 0.7 GBq. In differentiated thyroid cancer treatments, patient's urine was collected in storage tanks during the hospitalization. Measurements of external exposure at 1 m made every day were used to calculate the activity contained in the urine. The tank activity was always below 15 GBq, but always higher than 2 GBq. Obtained results show that effective doses to sewage workers, received from liquid discharges, can only be reduced to less than 10 μSv if storage tanks are installed. Without tanks, 157 μSv can be reached, above the constrain dose used in nuclear installations (100 μSv). Our calculations may be helpful to the regulatory authority to review the clinical radiation waste normative, especially in countries where the discharges are released directly into public sewage plants.

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case-control studies, and studies of prevalent cancers., Objective: To address this limitation, we evaluated the dose-response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study., Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514). Thyroid doses of I-131 were estimated based on individual radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models., Results: Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose-response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43-6.34], and the EAR per 10⁴ PY/Gy was 2.21 (95% CI, 0.04-5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size., Conclusions: I-131-related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies.

This study evaluated biokinetic behavior of radioiodine in the bodies of ten female adult patients, with well-differentiated thyroid cancer, treated with 131I post-near total thyroidectomy, for ablation of remnant thyroid. In vivo and in vitro bioassay analyses were performed from the first hour following radioiodine administration until minimum detection limits were reached. The retention of 131I in the body from day 1 to day 6 after the intake may be mathematically represented by an exponential decreasing curve, with an average biological half-life of approximately 0.81 d, with the exception of patients who presented thyroiditis. From day 6 to day 13, urinary excretion rates indicated an increased liberation of iodine. After 2 wk, the body retention of iodine followed an exponential decrease, with a half-life of about 15 d. The average whole-body dose for these patients was 0.27 Gy, as estimated through cytogenetic techniques.

Soon after the Bravo nuclear test at Bikini Atoll in the Marshall Islands on 1 March 1954, urine samples were collected for analysis of excreted radioactivity from native residents exposed to radioactive fallout on two atolls as well as from U.S. military personnel on a third atoll. The earliest acquired samples, obtained by the Los Alamos Scientific Laboratory (LASL), were assayed for various radionuclides and provided the first known measurements of (131)I in urine following exposure to fallout from a nuclear test. Over the course of 1954, many additional samples were collected by the LASL, as well as by the Atomic Energy Commission New York Operations Office's Health and Safety Laboratory and the Naval Radiological Defense Laboratory. Collectively, the groups sampled included Marshallese exposed on Rongelap and Ailinginae Atolls, American military weather observers temporarily resident on Rongerik Atoll, and sailors from the Japanese fishing vessel, the Lucky Dragon. While the bioassay measurement data and individual urine volumes have been crucial to various attempts to assess intakes of radioactivity and the related internal radiation doses among the Marshallese, those data have never been published in any peer-reviewed journal, but have been restricted to agency memoranda, laboratory reports, and summaries in some publications and book chapters. Reconstructions of internal doses to Marshallese in 1954 and in later years have depended on these data and, hence, they have considerable historical importance as well as importance to ongoing health risk projections for Marshallese. This paper presents much of the original data on urine volumes and radioactivity from the various assays of urine for radionuclides, and compares estimates of (131)I intakes made in 1954, 1985, 1987, and 2008.

Cholecystokinin, produced in the proximal small intestine, is a short acting satiating peptide hormone. CCK-10, before and after mono-iodination, was previously coupled to 10kDa polyethylene glycol (PEG). The formed conjugates PEG10kDa-CCK-10 and PEG10kDa-[(127)I]-CCK-10 show after i.p. administration to rats a sustained food intake reduction during 8h in comparison to 2h for free CCK-10. The present study examined the blood pharmacokinetics of this pharmacological interesting molecule by means of PEG10kDa-[(123)I]-CCK-10 following intravenous, intraperitoneal, intramuscular and nasal administration and the biodistribution after i.p. administration. HPLC analysis with radiometric detection allowed the differentiation between inorganic iodide and the intact tracer in blood. Blood kinetics after i.v. injection was fitted to a bi-exponential with a distribution half-life of 15 min and with an elimination half-life of 8 hours for intact PEG10kDa-[(123)I]-CCK-10. The biodistribution studies showed a higher accumulation of the tracer for all administration routes in organs expressing CCK receptors localized in the gastrointestinal tract such as pancreas, duodenum and small intestine. No indication of blood brain barrier crossing for the conjugate could be observed independently of the administration route. Main clearance was via the urinary pathway.

Background: Low-iodine diet is prescribed before (131)I administration in patients with differentiated thyroid cancer, although no study has properly quantified its clinical benefit., Objective: Our study aimed to evaluate the association between urinary iodine excretion (UIE) and (131)I ablation by correlating UIE with the rate of successful ablation., Patients: We retrospectively studied 201 differentiated thyroid cancer patients who had received (131)I therapy and posttherapy whole-body scan (WBS) for remnant ablation after either thyroid hormone withdrawal (THW group, n = 125) or recombinant human TSH (rhTSH group, n = 76). The outcome of thyroid ablation was assessed using two different criteria: no visible uptake at control WBS 8-12 months after ablation or no visible uptake plus undetectable stimulated serum thyroglobulin (Tg)., Results: According to the criterion of no visible uptake, 84.6% of the patients were successfully ablated, with no significant difference between THW and rhTSH groups. Mean UIE at the time of ablation was 132 +/- 160 microg/liter, not significantly different between patients of the THW and rhTSH groups. There was no significant difference in UIE between ablated or nonablated patients both in the whole group and the rhTSH or THW groups. According to the criterion of no visible uptake plus undetectable stimulated serum Tg (in anti-Tg negative patients) at control WBS 8-12 months after ablation, UIE was not significantly different in ablated and nonablated patients., Conclusions: Our study indicates that the body iodine content is not an important determinant of thyroid ablation, when preparing the patients with either THW or rhTSH.

The follow-up and treatment of thyroid cancer presents several aspects subject to discussion, such as its management in patients with End-Stage Renal Failure (ESRF). We present a patient with ESRF and papillary thyroid carcinoma, which had to be coordinated among different departments (Endocrinology, Nuclear Medicine, Nephrology and Physics and Radiation Protection). Both the diagnostic scintigraphy with (123)I and the ablative treatment with (131)I performed later were performed with the administration of rh TSH. The room in which the metabolic therapy was to be performed was prepared for the patient's periodic hemodialysis. The (131)I dose used was 80% of the usual dose. This made it possible to assure the therapeutic effect and that the patient's stay in hospital would only be for 5 days. Throughout the whole diagnostic and therapeutic process, no adverse effects attributable to rh TSH or radioiodine were observed. The coordination among the departments involved enabled an effective and safe process for the patient., (Copyright 2009 Elsevier España, S.L. y SEMNIM. All rights reserved.)

Objective: The objective of this study was to determine whether the use of recombinant human TSH (rhTSH) to stimulate radioiodine uptake after thyroidectomy is as efficacious as a period of withholding thyroid hormones, while at the same time avoiding hypothyroidism, reducing sick leave time and shortening the hospital stay., Design: Our aim was to compare the standard procedure of differentiated thyroid cancer treatment, which consists of thyroidectomy followed by 4 weeks of hypothyroidism and a conclusive ablative activity of (131)iodine, with a new shortened treatment in which l-thyroxine (T(4)) medication is initiated a day after thyroidectomy, followed by application of rhTSH stimulation and subsequent ablation a few days after surgery. We presumed our treatment to represent the most sophisticated strategy for the reduction in sick leave days overall without any reduction in safety or the efficacy of ablative therapy., Methods: Patients (n=25) were randomized either for surgery and rhTSH stimulation or surgery and l-T(4) abstinence before the first application of radioiodine. Ablation success was determined by neck ultrasound and serum thyroglobulin during follow-up. RhTSH receivers were monitored for an average of 635 days (s.d.+/-289) and patients in l-T(4) abstinence for an average of 624 days (s.d.+/-205). Both groups were statistically compared for significant differences in treatment efficacy, safety and overall time of sick leave., Results and Conclusions: Our shortened treatment proved to be equally efficacious and safe in comparison with the conventional therapy regimen. At the same time, it showed economic advantages through the reduction in average sick leave time from approximately 29 days (l-T(4) abstinence) down to approximately 6 days (rhTSH stimulation) as well as sustaining the patient's quality of life by the complete avoidance of hypothyroidism.

Background: In patients receiving (131)I for therapeutic purposes, diuretics are frequently used in an attempt to accelerate elimination of unbound radioiodine, reduce its adverse effects, and shorten the hospital stay. The aims of our study were to investigate the influence of furosemide therapy on urinary excretion of (131)I in patients with differentiated thyroid cancer (DTC), referred to radioiodine ablation after thyroidectomy, and to investigate whether diuretics are useful in daily practice in patients with DTC., Methods: Forty-three patients with DTC who had normal renal function and low (131)I uptake in cervical region (3.55 +/- 3.45%) were included in this study. The furosemide (20 mg) and potassium chloride (250 mg) were given orally to 23 patients 3 hours after the (131)I administration, and then q8h for 3 days. Twenty patients did not receive either furosemide or potassium chloride. After (131)I administration, the patients collected their urine for 3 days, and radioactivity of urine sample from each micturition was expressed as percentage of the administered dose. Radioactivity of blood samples was measured after 72 hours, and the values were corrected for decay of (131)I and expressed in relation to the administered dose. Initial whole-body measurement (immediately after (131)I administration) and the whole-body measurement after 72 hours were recorded for all patients. The 72-hour whole-body measurement was corrected for decay of (131)I, and expressed as a percentage of the initial whole-body measurement., Results: Urinary excretion of (131)I was significantly lower in the patients who were taking furosemide and potassium chloride compared with the control group. The whole-body measurements after 72 hours (13.22 +/- 6.55% vs. 8.24 +/- 3.39% of the initial; p < 0.01, respectively) and the blood radioactivity (34.66 +/- 24.84 vs. 11.64 +/- 8.32 cpm/mL per 1 MBq of administered (131)I, p < 0.01) were found to be unexpectedly higher in the patients who were taking furosemide and potassium chloride compared with the control group., Conclusion: Our results demonstrated that furosemide given as an adjuvant medication in patients with DTC causes a significant decrease in urinary excretion of radioiodine and its higher blood concentration. Therefore, furosemide should not be recommended as an adjuvant therapy to radioiodine ablation in patients with DTC previously iodine depleted by low-iodine diet.

Purpose: After contaminated radioactive linens were detected on the completion of intracranial brachytherapy for a patient episodically incontinent of urine, the systemic absorption of iodine 125 from the GliaSite Radiation Therapy System was studied. Diffusion and leakage of (125)I through the walls of the GliaSite balloon catheter have previously been reported to be negligible in both animal and human studies examining the radioactivity of urine during and after treatment. Our study estimated total systemic absorption based on activity defect measurements rather than using urinary excretion as a surrogate., Methods and Materials: Six patients treated with complete data were reviewed. The activity at the time of injection was compared to the activity recovered on completion of treatment after adjustment for decay., Results: By comparing the activity of (125)I infused with the activity recovered, 0.5-5.5% of infused (125)I remained unaccounted after adjusting for decay over the 4-day treatment period. The patient with contaminated hospital linens due to urinary incontinence had unaccounted activity of 2.3%. Comparisons of the volume of liquid (125)I and saline removed on completion to treatment to the volume originally instilled revealed no difference using hand-held syringes., Conclusions: The systemic absorption of (125)I is much greater than previously appreciated with potential clinical sequelae and safety concerns. GliaSite should be used with caution in patients incontinent of urine, and a Foley catheter should be placed to collect contaminated urine for incontinent patients.

This paper describes an unusual contamination incident that occurred during the treatment of a prostate cancer patient with seeds containing 125I. The incident became particularly interesting as the radiation safety procedures in place prior to the incident were, in fact, inappropriate for the type of incident that occurred, resulting in a series of response errors. Strands containing 108 125I seeds with a total activity of 1.61 GBq (43.6 mCi) were implanted into a patient's prostate and the patient was sent to the recovery room. A radiation survey detected radiation levels of up to 15 microR h(-1), 10 cm from the surface of the implantation needles. Multiple individuals entered the room and were potentially exposed to contamination. Contamination was detected in a sample of the patient's urine, indicating that one or more implanted seeds were leaking. Initial test results for staff showed that 12 of 15 had thyroid levels potentially above their corresponding minimum detectable activity levels, with calculated thyroid burdens ranging from 0.17 kBq to 0.94 kBq, but, subsequent measurements, using each staff member's thigh counts as background, suggested that no staff member had been contaminated. The patient showed high uptake of 125I in his neck 10 d following the incident, estimated to correspond to an initial thyroid burden of 58 kBq. The possibility of contamination was not immediately considered due to the suspicion of the more common problem of a misplaced source. The initial measurements suggesting thyroidal contamination in staff point to an error in our thyroid screening method.

Unlabelled: Poland, a country with mild/moderate iodine deficiency introduced an obligatory iodination salt system in 1996., Aim: To compare the results of radioiodine (131I) uptake after 5 h and 24 h with the activity of radioiodine used in the treatment of hyperthyroid patients with Graves' disease in the years 1995 and 2003., Patients, Methods: The marker of iodine content in the diet was urinary iodine excretion. 1000 randomly chosen patients (average age: 46 +/- 12 years) were included in the study. Every patient had routinely estimated radioiodine uptake after 5 h and 24 h and the activity of 131I was calculated using scintigraphy and ultrasonography of the thyroid gland. Urinary iodine excretion in samples from year 1995 and 2003 was also determined in some patients and healthy volunteers., Results: The iodine load in the diet increased from 66 microg (average) in the year 1995 to 115 microg in the year 2003. Thyroid radioiodine uptake was 40% lower in comparison with the results from 1995. The average activity of 131I given in the year 2003 (10 mCi) was about 40% higher than in the year 1995 (7 mCi)., Conclusion: There was significant negative correlation between higher iodine content in the diet and lower values of radioiodine uptake, which led to the application of the higher activity of 131I during treatment.

Aim: Urinary iodine excretion (UIE) provides information about iodine supply and release. In the present study we investigated effects of the application of different radioiodine isotopes on UIE in patients with differentiated thyroid carcinoma (DTC)., Patients, Methods: In 91 consecutive patients with DTC UIE, measured as iodine/creatinine ratio, was determined before and after application of 123I and 131I for diagnostic or therapeutic purposes. Additionally, remnant volume (V) was determined prior to therapy. Group A consisted of 33 patients with supposed successful ablation of DTC. These patients received 370 MBq 131I for diagnostic use and served as controls. 58 patients (group B) with remnants, relapses and metastases received 370 MBq 123I for diagnostics prior to therapy with 1.5-22.2 GBq 131I. Factors influencing individual changes in urinary iodine excretion (deltaUIE) were investigated by using non-parametric tests., Results: In group A UIE did not change significantly after application of 131I. As well, UIE remained unchanged after diagnostic application of 123I in group B. In contrast, UIE increased significantly already 24 h after therapeutic application of 131I in this group. In patients with small remnants (V < 2.5 ml) a significant but only moderate increase of UIE could be observed (average increase: 47 microg I/g crea). In patients with larger remnants, with relapses or metastases increase of UIE values was significant and more pronounced., Conclusions: It was confirmed that UIE increased significantly during radioiodine therapy in patients with DTC and radioiodine-accumulating tissue. The increase of UIE after therapeutic administration of radioiodine can be explained by the disintegrated thyroid follicles in thyroid remnants. The radioiodine-induced iodine release may be one reason for thyroid "stunning" even after application of diagnostic amounts of 131I.

Detection of perchlorate (ClO4-) in several drinking water sources across the U.S. has lead to public concern over health effects from chronic low-level exposures. Perchlorate inhibits thyroid iodide (I-) uptake at the sodium (Na+)-iodide (I-) symporter (NIS), thereby disrupting the initial stage of thyroid hormone synthesis. A physiologically based pharmacokinetic (PBPK) model was developed to describe the kinetics and distribution of both radioactive I- and cold ClO4- in healthy adult humans and simulates the subsequent inhibition of thyroid uptake of radioactive I- by ClO4-. The model successfully predicts the measured levels of serum and urinary ClO4- from drinking water exposures, ranging from 0.007 to 12 mg ClO4-/kg/day, as well as the subsequent inhibition of thyroid 131I- uptake. Thyroid iodine, as well as total, free, and protein-bound radioactive I- in serum from various tracer studies, are also successfully simulated. This model's parameters, in conjunction with corresponding model parameters established for the male, gestational, and lactating rat, can be used to estimate parameters in a pregnant or lactating human, that have not been or cannot be easily measured to extrapolate dose metrics and correlate observed effects in perchlorate toxicity studies to other human life stages. For example, by applying the adult male rat:adult human ratios of model parameters to those parameters established for the gestational and lactating rat, we can derive a reasonable estimate of corresponding parameters for a gestating or lactating human female. Although thyroid hormones and their regulatory feedback are not incorporated in the model structure, the model's successful prediction of free and bound radioactive I- and perchlorate's interaction with free radioactive I- provide a basis for extending the structure to address the complex hypothalamic-pituitary-thyroid feedback system. In this paper, bound radioactive I- refers to I- incorporated into thyroid hormones or iodinated proteins, which may or may not be bound to plasma proteins.

Background: Kidney function frequently is impaired in patients with cirrhosis; however, glomerular filtration rate (GFR) is difficult to estimate in these patients by using standard clinical markers. The aim of our study is to compare GFR calculated from renal clearance of iodine 125-labeled iothalamate ((125)I-iothalamate) with the plasma decay technique and the Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault (CG) prediction equations., Methods: We performed a cross-sectional study of patients with liver cirrhosis being evaluated for transplantation (50% Child's class C); 89% had ascites or edema and 44% were men aged 55 +/- 2 years. Average pretest blood urea nitrogen level was 16 +/- 2 mg/dL (5.7 +/- 0.7 mmol/L); serum creatinine, 1.0 +/- 0.1 mg/dL (88 +/- 9 micromol/L; range, 0.6 to 1.7 mg/dL [53 to 150 micromol/L]); plasma albumin, 3.14 +/- 0.16 g/dL (31.4 +/- 1.6 g/L); and total bilirubin, 4.0 +/- 0.7 mg/dL (67 +/- 11.3 micromol/L). Kidney function was measured by means of simultaneous plasma and renal clearance of (125)I-iothalamate (Glofil-125; Cypros Pharmaceutical Corp, Carlsbad, CA) and the MDRD and CG equations., Results: GFRs were 58.2 +/- 5.1 mL/min/1.73 m(2) by renal clearance of (125)I-iothalamate and 76.7 +/- 7.2 mL/min/1.73 m(2) by the plasma decay technique (+18.5 mL/min, or 32%; P = 0.0004). GFR by the MDRD equation was 76.9 +/- 7.8 mL/min/1.73 m(2) (+18.7 mL/min, or 32%; P = 0.0004 versus renal iothalamate; r(2) = 0.57). GFR by the CG equation was the least accurate (+30.1 mL/min, or 52%; P = 0.0001 versus renal iothalamate)., Conclusion: The current clinically used CG and MDRD equations to estimate kidney function in patients with cirrhosis and volume excess and the (125)I-iothalamate plasma decay technique are inaccurate because they overestimate GFR. It seems very unlikely that accurate and reliable formulas will be developed that are able to replace the formal measurement of GFR in patients with liver cirrhosis. Therefore, we conclude that despite the additional complexity, renal clearance techniques should be used to assess GFR accurately in patients with liver cirrhosis and ascites.

Aim: Elevated iodine intake is a serious problem in the diagnostic and therapeutic application of (131)iodine in patients with differentiated thyroid cancer. Therefore, iodine avoidance is necessary 3 months in advance. Additionally, endogenous stimulation requires withdrawal of thyroid hormone substitution for 4 weeks. Exogenous stimulation using recombinant human TSH (rhTSH) enables the continuous substitution of levothyroxine, which contains 65.4% of its molecular weight in iodine. Thus, a substantial source of iodine intake is maintained during exogenous stimulation. Although this amount of stable iodine is comparable to the iodine intake in regions of normal iodine supply, it may reduce the accumulation of radioiodine in thyroid carcinoma tissue. The aim of this study was to assess the iodine excretion depending on different ways of stimulation., Methods: Iodine excretion was measured in 146 patients in the long term follow up after differentiated thyroid carcinoma. Patients were separated into 2 groups, those on hormone withdrawal (G I) and rhTSH-stimulated patients on hormone substitution (G II)., Results: Iodine excretion was significantly lower in hypothyroid patients (G I, median 50 micro g/l, range: 25-600 micro g/l) than in those under levothyroxine medication (G II, median 75 micro g/l, 25-600 micro g/l, p <0.027). TSH in G I (median 57.0 micro U/ml, range: 14.4-183 micro U/ml) was significantly lower (p <0.001) than in G II (117 micro U/ml, 32.2-281 micro U/ml)., Conclusion: Iodine excretion was higher in patients under rhTSH-stimulation than after hormone withdrawal. This may indicate an increased iodine pool in rhTSH-stimulated patients (deiodination of levothyroxine), thus limiting the sensitivity of radioiodine scanning to the level of endogenous stimulation despite significantly higher TSH levels during rhTSH-stimulation.

This study describes one institution's experience with seed retrieval through the urinary tract and makes recommendations for cystoscopy and urine straining post prostate brachytherapy (PB). 1794 patients from two separate cohorts covering different time periods (early versus late) were analyzed. All patients were preplanned with a modified peripheral loading technique and implanted with preloaded needles (125I or 103Pd) under ultrasound guidance. A catheter was used to delineate the urethra during the volume study but was not used during the implant. All patients underwent post implant cystoscopy. All patients were instructed to strain their urine for seven days post implant and return any seeds to our center. In our experience, seed loss through the urinary tract is a common event after PB, occurring in 29.7% of patients and was more common in patients from the early cohort, those implanted with 125I seeds or those patients with prior transurethral resection of the prostate. Average seed loss per case, however, represents only 0.58% of total activity. We continue to recommend routine post implant cystoscopy for seed retrieval and periprocedural management. We no longer recommend that patients strain their urine at home after documenting a low rate of seed loss after discharge.

Objective: To determine the relationship between surface emission rate of gamma radiation and urine concentration of I131 (urine radioactivity) during the period 7 to 21 days after oral or SC administration of I131 to hyperthyroid cats., Animals: 47 hyperthyroid cats administered I131 PO and 24 hyperthyroid cats administered I131 SC., Procedure: A dose of I131 (1.78 to 2.04 X 10(2) MBq [4.8 to 5.5 mCi]) was administered orally. Surface emission at the skin adjacent to the thyroid gland on days 7, 10, 14, 18, and 21 and number of counts/30 s in a urine sample (1 mL, obtained via cystocentesis) on days 7, 14, and 21 after oral administration were measured. Effective half-life (T1/2E) was derived for each point. Surface emission thresholds for maximum urine radioactivity values were established. A dose of I131 (1.48 X 10(2) MBq [4.0 mCi]) was administered SC. Urine radioactivity and surface emission rates for SC administration were compared with values for oral administration., Results: The T1/2E for surface emissions and urine radioactivity progressively increased toward values for physical T1/2 over time. The T1/2E for surface emissions was 2.19 to 4.70 days, and T1/2E for urine radioactivity was 2.16 to 3.67 days. Surface emission rates had a clinically useful threshold relationship to maximum urine concentrations of I131., Conclusions and Clinical Relevance: Surface emission rates for cats administered I131 appeared useful in determining upper limits (threshold) of urine radioactivity and are a valid method to assess the time at which cats can be discharged after I131 administration.

Low-iodine diet has been employed to achieve iodine depletion prior to radioiodine (RI) therapy. However, treatment with diuretics may be more effective than low-iodine diet in causing iodine depletion and subsequent increase in RI uptake by the thyroid. Fifty-five patients with non-toxic goitre were given 0.20 MBq RI p.o. on the first day of the study and thyroid uptake was measured. In 15 patients, a low-iodine diet was started and continued for 14 days. The remaining 40 patients received furosemide 40 mg/day orally for 5 days with an unrestricted diet. On the 15th day of the study, all patients were given 0.20 MBq RI p.o. and thyroid RI uptake was measured again. Additionally, 24-h urinary iodine excretion and RI clearance were measured on the 1st and 6th days in 21 patients from the furosemide group and on the 1st and 15th days in eight patients from the diet group. Furosemide administration led to a 58.40% increase in iodine uptake over the baseline value, which was significantly higher than the increase caused by low-iodine diet (17.22%) ( P<0.0001). Urinary excretion of RI decreased in both groups similarly (furosemide, 29.45%; low-iodine diet, 21.06%; P=0.33). Iodine clearance also decreased in each group similarly (10.61% vs 7.53%, P=0.53). Treatment with furosemide prior to administration of RI increases the uptake of RI by the thyroid more effectively than does low-iodine diet.

To synthesize a biotin radiopharmaceutical that clears rapidly, dendrimer was used as a carrier and conjugated with succinimidyl 3-[(125)I]iodobenzoate and tetrafluorophenyl norbiotinamidosuccinate. Then, succinic anhydride was used to reduce its pI. In mice, the non-succinylated product showed high liver (67% ID/g) and kidney (44% ID/g) uptakes and whole-body retention (94% ID) at 20 min that persisted for 12 hr. The corresponding organ uptakes (22% and 11% ID/g) and the whole-body retention (47% ID) were drastically reduced by succinylation (p<0.0001). Lysine co-injection further lowered renal uptake.

Low-molecular-weight polyethylenimine (LMW-PEI) was synthesized by the acid-catalyzed, ring-opening polymerization of aziridine and compared with commercially available high-molecular-weight PEI (HMW-PEI) of 25 kDa. Molecular weights were determined by size-exclusion chromatography in combination with multi-angle laser light scattering. The weight average molecular weight (M(w)) of synthesized LMW-PEI was determined as 5.4+/-0.5 kDa, whereas commercial HMW-PEI showed a M(w) of 48+/-2 kDa. DNA polyplexes of LMW-PEI and HMW-PEI were characterized with regard to DNA condensation (ethidium bromide fluorescence quenching), size (photon correlation spectroscopy) and surface charge (laser Doppler anemometry). Compared with HMW-PEI, DNA condensation of LMW-PEI was slightly impaired at lower N/P ratios. Complexes with plasmid DNA at a N/P ratio of 6.7 showed significantly increased hydrodynamic diameters (590+/-140 vs. 160+/-10 nm), while the zeta-potential measurements were similar (23+/-2 vs. 30+/-3 mV). The cytotoxicity of LMW-PEI in L929 fibroblasts was reduced by more than one order of magnitude compared with HMW-PEI, as shown by MTT assay. LMW-PEI exhibited increased transfection efficiency in six different cell lines. Reporter gene expression was found to be increased by a factor of 2.1-110. The pharmacokinetics and biodistribution of 125I-PEI in mice were similar for both molecular weights with an AUC of ca. 330+/-100% ID/ml min. Approximately half of the injected dose accumulated in the liver. LMW-PEI proved to be an efficient gene delivery system in a broad range of cell lines. Due to differences in polyplex structure, as well as its relatively low cytotoxicity, which makes the application of high N/P ratios possible, LMW-PEI appears to possess advantageous qualities with regard to transfection efficiency over PEI of higher molecular weight.

Unlabelled: We evaluated the use of radiolabeled 4-iodo-L-meta-tyrosine as an amino acid transport marker. The pharmacologic features of this compound, particularly the biodistribution and excretion, were examined by conducting in vivo and in vitro studies using 4-(125)I-iodo-L-meta-tyrosine (4-(125)I-mTyr). Results obtained for L-(14)C-Tyr and 3-(125)I-iodo-alpha-methyl-L-tyrosine ((125)I-IMT) were used for comparison., Methods: In vivo biodistribution studies of 4-(125)I-mTyr were performed in male ddY mice. Urinary excretion of 4-(125)I-mTyr and (125)I-IMT with administration of probenecid was studied. Local distribution of 4-(125)I-mTyr and (125)I-IMT in kidney was visualized by autoradiography. We performed metabolite analysis of 4-(125)I-mTyr in mice. For in vitro studies, reabsorption mechanisms of 4-(125)I-mTyr were compared with those of (125)I-IMT and the parent L-(14)C-Tyr using superconfluent monolayers of the porcine kidney epithelial cell line LLC-PK(1) in medium containing inhibitor (L-Tyr, D-Tyr, and 2,4-dinitrophenol), in Na(+)-free medium, and at 4 degrees C., Results: 4-(125)I-mTyr demonstrated high accumulation in the pancreas and kidney and comparable brain uptake to that of (125)I-IMT. Blood clearance of 4-(125)I-mTyr was faster than that of (125)I-IMT. Three hours after administration, >70% of 4-(125)I-mTyr was excreted via the urine, whereas <5% was found in the feces. Renal autoradiography revealed moderate accumulation of 4-(125)I-mTyr and high accumulation of (125)I-IMT in the renal cortex. Probenecid further reduced accumulation of 4-(125)I-mTyr and (125)I-IMT in the kidney as well as urinary excretion. At 30 min after tracer injection, intact free 4-(125)I-mTyr accounted for >98.1% of the total present in kidney and >96.3% in urine. Protein incorporation was not observed. Uptake of 4-(125)I-mTyr into LLC-PK(1) cell monolayers was remarkably reduced by 5 mmol/L L-Tyr (4.6%) and incubation at 4 degrees C (15.6%) but was reduced by 5 mmol/L D-Tyr (50.0%). L-(14)C-Tyr and (125)I-IMT showed similar results; however, uptake of (125)I-IMT was enhanced by 0.1 mmol/L 2,4-dinitrophenol (165.1%), an inhibitor of generation of energy-rich phosphates., Conclusion: The artificial amino acid 4-(125)I-mTyr demonstrated high metabolic stability, rapid blood clearance, rapid urinary excretion, and similar biodistribution to other radiolabeled L-Tyr analogs. 4-(125)I-mTyr can be a competitive substrate of L-Tyr reabsorption. However, 4-(125)I-mTyr demonstrates different pharmacologic features than those of (125)I-IMT, particularly in renal handling. 4-(125)I-mTyr may potentially be applied as a new amino acid transport marker.

The handling of a liquid radioactive source is a procedure that is uncommon for the average clinical medical physicist. A newly approved treatment device utilizes high activities of liquid I-125 solution as the source of radiation. The radiation safety issues and our experience utilizing high activity liquid I-125 sources are presented. To date we have treated 22 patients with infused activities ranging up to 26.8 GBq (724 mCi). The careful manipulation of such solutions is important to maintain a safe environment for the patients and the involved medical staff., (2003 American College of Medical Physics.)

Human thyroids collected from Gomel in Belarus, sheep thyroid from Jutland and human urine from Zealand in Denmark were analysed for 129I and 127I concentrations. The ratios of 129I/127I in human thyroid in Gomel are 2.65-11.0 x 10(-9) with an average of 7.21 x 10(-9), which is one order of magnitude higher than those from Asia and South America (10(-10)), but significantly lower than those observed in west Europe (10(-8)). A weak negative correlation (P < 0.05) between 129I/127I ratio in human thyroid and the age of the subjects was observed in Gomel. The average ratio of 129I/127I in sheep thyroids from Jutland of Denmark is 1.81 x 10(-7), which is two orders of magnitude higher than those in south hemisphere, and Asia. It is also significantly higher than those observed in other west European countries before 1984 and that in human thyroid in Gomel. The high thyroid 129I level in Jutland is attributed to the release of reprocessing plants in France and UK. The 129I/127I ratios in human urine in Zealand of Denmark are 0.86-2.86 x 10(-8). The possibility of using urine 129I to evaluate the thyroid exposure to 129I is investigated., (Copyright 2002 Elsevier Science B.V.)

A dose reconstruction study was performed for personnel occupationally exposed to 131I in radiopharmaceutical production, during the years 1981 to 1994, with the objective of estimating committed effective doses and critically reviewing the main causes of their exposures. The workers were selected from a group responsible for the production, labelling and distribution of all radiopharmaceutical material in Brazil. Best estimates of intakes and doses were derived from the examination of the individual monitoring records and the reports from the radiation protection supervisor, complemented by interviews with the workers and with radiation protection officers. Over this time period workers had chronic as well as acute intakes of 131I. Committed effective doses were found to be dependent on the task performed by the worker and the site of operation and inversely correlated with the amounts of iodine handled. Intakes in general were a consequence of inadequate radiation protection control.

Background: The aim of this study was to examine the biodistribution of (131)I-herceptin in C3H/Bi mice with transplantable mammary adenocarcinoma with a high frequency of C-erbB2 receptor expression., Material and Methods: Mice C3H/Bi with subcutaneously transplanted mammary adenocarcinoma were used as animal model to study the interaction between C-erbB2 receptor and hercepin, a humanized anti-C-erbB2 monoclonal antibody. The expression of the gene encoding C-erbB2 receptor in the tumours was studied by the RT-PCR technique., Results: Expression of this gene was found in 66% of the studied cases. Similarly, the presence of the C-erbB2 receptor in 77% of the tumours was detected by a Western blot analysis with the use of herceptin. Biodistribution experiments of iodine-labelled herceptin in mice C3H/Bi with adenocarcinoma revealed its maximal accumulation in the tumours at 48 hours since the i.v. injection (7% ID/g). The tumour/muscle radioactivity ratio reached its highest value (above 20) also at 48 hours after the injection., Conclusions: C3H/Bi mice with this adenocarcinoma may be a good experimental model to study herceptin, or its fragments, labelled with different radionuclids for preliminary evaluation of their usefulness in the therapeutic and diagnostic aspects of breast cancer.

The native chimeric human-mouse anti-CD20 antibody IDEC-C2B8 (rituximab) is therapeutically applied in relapsed non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the distribution and pharmacokinetics of iodine-131 labelled rituximab in humans for radioimmunotherapy of relapsed CD20-positive NHL. Thirty-five patients with relapsed NHL were administered 20-40 mg rituximab labelled with 250 MBq (131)I. Biodistribution was determined by the gamma camera whole-body scans, whole-body probe measurements and the analysis of serial blood and urine samples. Dosimetry was performed using the MIRDOSE 3 program. Antibody administration was well tolerated. The whole-body activity showed a mono-exponential decrease with a wide range of effective half-lives, the mean value (88 h) being significantly longer than the half-life of its murine counterpart, tositumomab. This led to appropriately higher dose factors for the whole body and organs. Activity was excreted mainly through the kidneys. Normal organs showed decreasing ratios of organ to whole-body activity over time, whereas the tumour tissue presented different kinetics, with increasing ratios of tumour to whole-body activity as evidence for specific antibody binding. It is concluded that (131)I-labelled rituximab is suitable for pretherapeutic dosimetry. Due to the wide range of whole-body and organ dose factors, individual dosimetry is necessary for radioimmunotherapy with (131)I-labelled rituximab. The therapeutic activities of (131)I-labelled rituximab required to deliver similar doses should be lower than those of its murine counterpart.

This study was undertaken to improve the renal clearance and tumor targeting properties of 99mTc-labeled humanized anti-Tac (HuTac) monoclonal antibody Fab fragments using two chemical approaches: 1) labeling with a renal secretion agent 99mTc-mercaptoacetyltriglycine (MAG3) and 2) lowering its isoelectric point (pI) by acylation. HuTac Fab (3.3 mg/mL) was reacted with a trifluorophenyl ester (TFP) of 99mTc-MAG3 alone or was additionally reacted with TFP-glycolate to reduce the pI. In Balb/c mice, 99mTc-MAG3-Fab (pI > 9.3) rapidly accumulated in the kidneys (177% injected dose [ID]/g at 15 min) and then gradually cleared out of the kidneys. In contrast, the glycolation (pI 4.6 approximately 6.6) drastically reduced the renal uptake (31% ID/g) and also the whole-body retention (82% ID vs 101% for the nonglycolated) at 15 min, indicating that the glycolated 99mTc-MAG3-Fab (pI 4.6 approximately 6.6) was rapidly excreted. The glycolated remained in the blood longer than the nonglycolated (1.2% vs 0.3% ID/g at 360 min), but this effect was less drastic than the effect shown on the renal uptake. In nude mice bearing receptor-positive (ATAC4) tumors, the glycolated 99mTc-MAG3-Fab increased the peak tumor uptake to 14.8% ID/g from 8.3% ID/g for 99mTc-MAG3-Fab, whereas the glycolation resulted in a drastic reduction of the renal uptake at 15 min. We demonstrated that the renal clearance and the tumor targeting of Fab could be optimized by chemical modifications.

Background: In I-131-MIBG therapy, I-131-iodide can be released from the I-131-MIBG molecule. Hypothyroidism might result from the undesirable irradiation of the thyroid gland. To prevent this, stable iodide such as potassium iodide (KI) is given to oversaturate the thyroid before I-131-MIBG is administered., Procedure: In the present study, the incidence of hypothyroidism (elevated TSH) was correlated with the thyroidal uptake of I-131 and dose (MIRD dosimetry) after 35 individual treatments in ten patients. Iodine-131-MIBG therapy was performed using a modified dosage of 1.9-11.1 GBq (50-300 mCi) IV. Premedication with KI was done as recommended with a dose of 100 mg KI orally from 2 days before until 4 weeks after I-131-MIBG., Results: The absorbed thyroidal dose amounted to a very variable range of 0.2 (patient # 1) up to 30.0 (patient 3) Gy with 7.1 +/- 7.9 Gy per treatment and 24.1+/- 19.2 Gy per patient (mean+/- SD), despite the same and compliantly taken KI premedication protocol. Up to now, 4/10 or 40% of patients have developed hypothyroidism after a mean follow-up period of 11 months and a mean total administered dose of 18.7 GBq (505 mCi). A trend towards higher thyroidal doses was seen in the hypothyroid patients., Conclusions: This study observes a general high inter- and intra-individual variability in radio-iodide uptake in the thyroid after I-131-MIBG therapy despite KI premedication, as well as possible occurrence of hypothyroidism. A dose-response relationship needs confirmation on a larger cohort of patients to reach statistical value. An alternative thyroid cytoprotection strategy for possible long-term survivors may be considered., (Copyright 2002 Wiley‐Liss, Inc.)

In Japan, a new guideline for the release of patients administered 131I was issued by the Ministry of Welfare on June, 1998: The dose rate is under 30 microSv/h at 1 m or the activity in the body is under 500 MBq. This study was designed to set the appropriate isolation period enough to satisfy these limits. A total of 28 patients with the history of total thyroidectomy and metastasis were selected for this study. In these patients, 28 patients were treated with oral administration of 3.7 GBq of Na131I (72 times), and one of 28 patients was once treated with 5.55 GBq of Na131I. Two of them were also received a total of 4 courses of a split dose therapy of 3.7 GBq of Na131I (740 MBq once a week for 5 consecutive weeks = one course). Measurements of the external exposure dose (microSv/h) at 1 m and the urinary excretory radioactivity (MBq) were performed at various times. There was a good correlation of the external exposure dose between standing (x microSv/h) and sitting (y microSv/h) postures (y = 0.99x + 0.406, r = 0.99, p < 0.0001, n = 169). The difference in the external exposure dose before and after urination (x microSv/h) had a significant correlation with the urinary excretory radioactivity (y MBq); y = 16.6x + 24.8, r = 0.96, p < 0.001, n = 41. Also, there was a significant correlation between the predicted value of residual radioactivity in the body (y' MBq) and the external exposure dose (x' microSv/h); y' = 20.8x' + 31.5, r = 0.98, p < 0.001, n = 77. In the patients treated with 3.7 GBq of Na131I, the mean and S.D. values of the external exposure dose (microSv/h) changed as follow: After 6 hr, 168 +/- 40; 24 hr, 52 +/- 23; 48 hr, 20 +/- 15; 72 hr, 10 +/- 9; and 96 hr, 8 +/- 9. The percentages of the patients satisfied the new guideline were as follow; 21.7% at 24 hr, 81.2% at 48 hr and 100% after 72 hr. Therefore the 3-day isolation is sufficient for the patients administered 3.7 GBq of Na131I.

U.S. NRC Regulatory Guide 8.39 provides for the release of patients treated with 131I provided that predetermined calculations indicate that no member of the public will receive a total dose equivalent in excess of 5 mSv (500 mrem). When this condition cannot be met or there are other reasons for keeping the patient hospitalized after treatment, control of contamination and exposure from the patient must be taken into consideration. If the patients are hospitalized following treatment, decontaminating the patient's room after discharge and controlling the exposure potential from the patient are considerations for the hospital radiation safety staff. This paper reviews the experiences from fifty patients treated as inpatients over the past two years.

The iodo derivative of histamine labelled with 125I has been used for many years to prepare tracers used in RIA systems. The aim of this study was to evaluate radioiodinated histamine as a potential isotope carrier for in vivo applications. The biological behaviour of radioiodinated histamine has been investigated in rodents. The observed absence of any specific iodohistamine uptake by a critical organ or tissue promises a very quick distribution of the iodohistamine in soft tissues, and a rapid rate of whole-body clearance via the urinary tract (e.g. over 50% of the injected dose (ID) during the first hour after administration). In spite of moderately low in vitro stability of iodohistamine in serum, biodistribution studies in rodents have not shown any significant release of iodine from the parent molecule in the whole animal. Low uptake was observed in the thyroid (e.g. 0.22 and 0.11% ID at 1 and 2 h after administration to rats), and not more than 3% of injected activity was detected in the stomach in all of the biodistribution experiments. Moreover, our results refute any possibility of competition between histamine and iodohistamine for receptor binding sites, and suggest that radioactive mono-iodohistamine may be used successfully to develop some new radiolabelled bioactive molecules with potential application in vivo.

[76Br]Bromodeoxyuridine ([76Br]BrdU) might allow a determination of proliferation in vivo using positron emission tomography (PET), but only with consideration of organ nonspecific radioactivity constituted by [76Br]bromide. A first study assessed the potential of diuretics to eliminate [76Br]bromide. [76Br]Bromide was injected in the vein of rats and different diuretic combinations were given. Urine was collected and radioactivity measured. Torasemide plus sodium chloride gave better 76Br elimination than the other diuretics. In a second experiment, rats were given [76Br]BrdU. After the radioactivity injection, the rats of the treatment group were given torasemide plus NaCl. At 44 h after the radioactivity injection, the radioactivity concentration and the fraction incorporated into DNA were measured in different organs. Using diuretics, the elimination of [76Br]bromide was increased. The radioactivity decreased 30-50% in most of the organs but the highest radioactivity uptake was found in the organs with more active DNA synthesis. This method may facilitate the use of [76Br]BrdU as a tracer for DNA synthesis using PET.

Unlabelled: 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.

A useful correlation between maximum thyroid uptake and radioiodine urine levels at different times after exposure was developed in order to determine when the intervention with an adequate blocking agent might still be effective. In an animal model (dog), six different doses were administered in the range of 100-600 kBq. The best correlation was found between the 125I uptake after 48 h (T-48) and urine radioactivity 4-6 h (U-4, U-5, U-6) after exposure. For the case of U-4, the equation Y(T-48) = 0.790 X(U-4) + 2.973 (r = 0.974 with a level of significance of p < 0.001) was obtained. An analogous study, carried out in humans (n = 20) to whom 1311 was administered, showed a similar correlation and level of significance: Y(T-24) = 1.162 X(U-4)+3.263 (r = 0.926; p < 0.001). The validity of this correlation was confirmed in four volunteers who received small doses of 125I(25-100 kBq), with good agreement between measured and extrapolated thyroid uptake and a mean difference of less than 10% (CV = 16.2%). Three different blocking agents were then tested in the same dog: potassium iodide, potassium perchlorate, and a thionamide (Tapazole). The blocking action of the first two compounds was about 90%, as opposed to only 48% for the third compound. Potassium iodide was chosen for its limited side effects and more universal utilization. The final study, carried out with four different doses, indicated that 25 mg of KI is the ideal amount to be administered to the dog. This corresponds to approximately 100 mg for a 70 kg human being (i.e., 1.4 mg kg(-1)). This dose, when administered to a volunteer 4 h after exposure, provided a thyroid blocking of 68%.

An underground system of tanks was installed to delay the discharge of 131I waste from the thyroid therapy unit to the on-site sewage treatment plant. As a consequence, the level of radioactivity discharged to sewage has fallen by a factor of 530, reducing the radiation dose to hospital and auxiliary service staff. Cancer patients are no longer required to collect their urine, hence increasing the hygiene for all concerned. A model was developed of iodine waste which estimates the dose rate above the delay tanks and the activity of iodine discharged. The maximum effective dose to a member of the public due to the holding tanks is 40 microSv.year-1. There is now better management of the radioactive waste from the iodine therapy ward.