Biokinetics of iodine-131 in rat thyroid following lead and lithium supplementation

The impact of lead as an environmental pollutant on the I-131 uptake and retention in rat thyroid was assayed alone and in combination with lithium treatment. Lead treatment significantly stimulated the 2- and 24-h uptake of I-131 in the thyroid, and the 24-h uptake showed the maximum stimulation after 3 mo of lead treatment. On the contrary, lithium supplementation reduced the uptake significantly and the maximum decrease was noticed after 2 mo of lithium administration. Further, simultaneous lead and lithium treatment resulted in more pronounced increase in the uptake of I-131 by the thyroid, which was maximum after 3 mo of combined treatment. The thyroidal biological half-life of I-131 (T _biol) was found to be increased significantly following lead and lithium treatments when given separately. Interestingly, combined lead and lithium treatment given up to 2 mo further prolonged theT _biol of I-131, thus reflecting its increased retention.     

Thyroid cancer after diagnostic administration of iodine-131 in childhood.

Hahn, K., Schnell-Inderst, P., Grosche, B. and Holm, L-E. Thyroid Cancer after Diagnostic Administration of Iodine-131 in Childhood. Radiat. Res. 156, 61-70 (2001).To determine the carcinogenic effects of diagnostic amounts of (131)I on the juvenile thyroid gland, a multicenter retrospective cohort study was conducted on 4,973 subjects who either had been referred for diagnostic tests using uptake of (131)I (n = 2,262) or had had a diagnostic procedure on the thyroid without (131)I (n = 2,711) before the age of 18 years. Follow-up examinations were conducted after a mean period of 20 years after the first examination in 35% of the exposed subjects (n = 789) and in 41% of the nonexposed subjects (n = 1,118). Iodine-131 dosimetry of the thyroid was carried out according to ICRP Report No 53, and the median thyroid dose was 1.0 Gy. In the exposed group, two thyroid cancers were found during 16,500 person-years, compared to three cancers in the nonexposed group during 21,000 person-years. The relative risk for the exposed group was 0.86 (95% CI: 0.14-5.13). The study did not demonstrate an increased risk for thyroid cancer after administration of (131)I in childhood.     

Effect of short-term and long-term lithium treatment on uptake and retention of iodine-131 in rat thyroid

No significant change occurred in the uptake by the thyroid of male Wistar rats of a standard dose of carrier-free 131I administered intraperitoneally and its retention by the thyroid, as measured by biological and effective half-life, after feeding these rats a powdered pelleted diet containing lithium carbonate (1.1 g per kg of diet) for 7 days. However, continuing this diet for 10 days inhibited thyroid uptake and increased the retention of 131I. Uptake remained suppressed for up to 4 months after lithium treatment and continuing this treatment for 6 months did not result in any significant change in 131I uptake by the thyroid. Lithium treatment for 10 days increased the biological and effective half-life of 131I in the thyroid and this increase continued for the 6 months treatment period. The dose of 131I delivered to the thyroid was significantly lower after 10 days and 1 month of lithium treatment but there was no change in this dose after 2 and 4 months of treatment. However, there was a significant increase after 6 months.     

Mutagenicity of diagnostic and therapeutical doses of radiopharmaceutical iodine-131 in Wistar rats

Iodine-131 (¹³¹I) is a radioisotope used for the diagnosis and treatment of thyroidal disorders such as hyperthyroidism and cancer. During its decay, ¹³¹I emits beta particles and gamma rays; its physical half-life is 8 days, and it is accumulated preferentially in the thyroid tissue. This study aimed to evaluate the cytotoxicity and mutagenicity of diagnostic and therapeutic doses of ¹³¹I using bone marrow cells of rats treated in vivo in a test system with a single dose by gavage. Concentrations of 5, 25, 50 and 250 μCi in 1 ml of water were used, and after 24 h, the animals were killed. Also, a concentration of 25 μCi/ml of water was used, and the animals were killed after 5 days. The results showed that no concentration of ¹³¹I was cytotoxic and that all concentrations were mutagenic. As a result, there was no statistically significant difference detected by the χ² test in the induction of chromosomal aberrations between the different doses. Thus, the present study demonstrated a significant increase in chromosomal aberration in bone marrow cells exposed to ¹³¹I regardless of the dose or the treatment time.     

Postradiation changes in the thyroid gland and skeletal muscle after exposure to iodine-131

The functional status of rat skeletal muscles was studied at dormancy and during the intensive muscular work under conditions of repeated administration of iodine 131 in doses causing reversible and irreversible damages to thyroid gland (the absorbed doses were from 0.27 to 266 Gy). The biochemical changes in muscles were transient; they correlated with the thyroid gland status and lifetime of animals and were displayed during the first 15 days and 2-12 months after the start of the isotope injection.     

Diphasic effect of thyrotropin on the uptake and absorption of iodine-131 by thyroid cell culture]

The studies were performed on the primary culture of thyroid cells of newborn pigs. It was shown that thyroid-stimulating hormone (TSH) within the first 12th of its action inhibited uptake and organification of iodine-131. A negative influence of TSH on 131I uptake was retained both with its simultaneous introduction into the culture medium and with 30 min interval as well as when conducting experiments on the 1st, 3d, 5th and 7th days of cultivation. Previous 72h incubation with TSH sufficient for activation of all the links of iodine transport caused an increase in 131I uptake and organification.     

Graves' disease and atrial fibrillation: the case for even higher doses of therapeutic iodine-131.

Seventy five consecutive patients with Graves'' disease complicated by atrial fibrillation were given a large single therapeutic dose of 600 MBq (16.2 mCi) iodine-131 in an effort to control their hyperthyroidism rapidly and thus restore sinus rhythm. Patients were initially followed up every three months after treatment and then at yearly intervals. The mean period of follow up was 3.1 years. A total of 44 of the patients became hypothyroid and 31 euthyroid, and 33 (75%) and 14 (45%) of these patients, respectively, reverted to sinus rhythm (p less than 0.01). Of the 33 who became hypothyroid and reverted to sinus rhythm, 30 had developed the hypothyroidism within six months after treatment. These results are a strong case for increasing the dose of radioiodine in patients with Graves'' disease complicated by atrial fibrillation in an effort to speed the onset of thyroid failure and thus maximise the rate of reversion to sinus rhythm.     

A comparison of physical and cytogenetic estimates of radiation dose in patients treated with iodine-131 for thyroid carcinoma.

Physical and cytogenetic estimates of the whole-body radiation doses have been compared in 11 patients receiving large doses of iodine-131 for the treatment of thyroid carcinoma. The physical estimate was based on the measurement of thyroid uptake, of the plasma activity variation, and of urinary activity. The cytogenetic estimate was obtained from the analysis of chromosome aberrations in peripheral blood lymphocytes. Good agreement between the estimates was observed in patients whose thyroid glands had previously been ablated by radioiodine. In patients who had varying degrees of thyroid function, there were considerable differences between the estimates with the cytogenetic value always being higher. It is suggested that these differences might be due in part to non-uniform irradiation of lymphocytes by local sources of activity in the thyroid and in the liver.     

Formation of micronuclei and of clastogenic factor(s) in patients receiving therapeutic doses of iodine-131

The micronucleus (MN) assay in peripheral blood lymphocytes was applied to assess the genotoxic potential of a single dose of iodine-131 (131I) given to six patients for ablation of thyroid remnants after total thyroidectomy. Lymphocytes were taken at various times after 131I therapy (from 2 to 180 days), and evaluated for the presence of MN in the binucleated cells identified after blocking cytokynesis with cytochalasin B. The presence of ultrafiltered, low-molecular weight, clastogenic factor(s) (CFs) in the plasma of 11 patient undergoing 131I therapy was also sequentially assessed.A significantly increased MN frequency was observed in lymphocytes of patients as soon as the first sampling time (2 days after 131I therapy), multifactor analysis of variance (MANOVA): P<0.0001, peaking at day 7 at almost four-fold the spontaneous frequency observed in the pre-therapy samples. MN frequency slowly declined thereafter, reaching the baseline levels at the 180-day time point. When tested against peripheral blood lymphocytes from a healthy donor, the ultrafiltered CFs obtained from 11 patient's plasma induced a significant increase of the MN frequency peaking at day 15. Thereafter, a slow MN frequency decline was observed and the baseline frequency was reached after 180 days. A significant relationship was found between the MN frequency observed in lymphocytes of patients after 131I therapy and the genotoxic CFs activity present in their plasma (P=0.019).These findings suggest that 131I induces a significant increase in the MN frequency of peripheral blood lymphocytes, as well as the formation of transferable CFs which persist for at least 60 days after administration of the radionuclide. The presence of these CFs might be responsible of chromosome aberrations often observed in cultured lymphocytes following X-ray exposure. The possibility of reducing the genotoxic activity of radionuclide therapy by chemoprevention of CFs with antioxidant drugs remains to be explored.