Essentiality, relevance, and efficacy of adjuvant/combinational therapy in the management of thyroid dysfunctions.

Thyroid dysfunction is the most prevalent endocrine disorder worldwide having an epidemiology of 11% in Indians, 4.6% in the United Kingdom, and 2% in the United States of America among the overall population. The common thyroid disorders include hypothyroidism, hyperthyroidism, Hashimoto's thyroiditis, and thyroid cancer. This review briefly elaborates the molecular regulation and mechanism of thyroid hormone, and its associated thyroid disorders. The thyroid hormones regulate critical biochemical functions in brain development and function. Hypothyroidism is mainly associated with dysregulation of cytokines, increased ROS production, and altered signal transduction in major regions of the brain. In addition, it is associated with reduced antioxidant capacity and increased oxidative stress in humans. Though 70% of thyroid disorders are caused by heredity, environmental factors have a significant influence in developing autoimmune thyroid disorders in people who are predisposed to them. This drives us to understand the relationship between environmental factors and thyroid dysregulated disorders. The treatment option for the thyroid disorder includes antithyroid medications, receiving radioactive iodine therapy, or surgery at a critical stage. However, antithyroid drugs are not typically used long-term in thyroid disease due to the high recurrence rate. Adjuvant treatment of antioxidants can produce better outcomes with anti-thyroid drug treatment. Thus, Adjuvant therapy has been proven as an effective strategy for managing thyroid dysfunction, herbal remedies can be used to treat thyroid dysfunction in the future, which in turn can reduce the prevalence of thyroid disorders.

Ultrasound-guided implantation of radioactive 125I seed in radioiodine refractory differentiated thyroid carcinoma.

BACKGROUND: Treatment for radioiodine refractory differentiated thyroid carcinoma (RR-DTC) is challenging. The purpose of this study was to assess the efficacy and safety of ultrasound-guided implantation of radioactive 125I-seed in radioiodine refractory differentiated thyroid carcinoma. METHODS: Thirty-six cervical metastatic lymph nodes (CMLNs) diagnosed with RR-DTC from 18 patients were enrolled in this retrospective study. US and contrast-enhanced ultrasound (CEUS) examinations were performed before implantation. Follow-up comprised US, CEUS, thyroglobulin (Tg) level and routine hematology at 1-3, 6, 9 and 12 months and every 6 months thereafter. The volumes of the nodules were compared before implantation and at each follow-up point. The volume reduction rate (VRR) of nodules was also recorded. RESULTS: The median volume of the nodules was 523 mm3 (148, 2010mm3) initially, which decreased significantly to 53mm3 (0, 286mm3) (P < 0.01) at the follow-up point of 24 months with a median VRR as 95% (86,100%). During the follow-up period (the range was 24-50 months), 25 (69%) nodules had VRR greater than 90%, of which 12 (33%) nodules had VVR ≈ 100% with unclear structures and only 125I seed images were visible in the US. At the last follow-up visit, the serum Tg level decreased from 57.0 (8.6, 114.8) ng/ml to 4.9 (0.7, 50.3) ng/ml, (P < 0.01). CONCLUSION: US-guided 125I seed implantation is safety and efficacy in treating RR- DTC. It could be an effective supplement for the comprehensive treatment of thyroid cancer.

Multikinase inhibitors for the treatment of radioiodine refractory thyroid cancer: what have we learned from the 'real-world' experience?

PURPOSE OF REVIEW: Several molecularly targeted drugs for treating radioiodine resistant differentiated thyroid carcinomas (RAIR-DTC) have been identified. Among these, sorafenib and lenvatinib have been approved for clinical use in many countries. The present review will analyze efficacy and safety 'real-world' data (RWD) emerging after their commercialization. RECENT FINDINGS: RWDs confirmed sorafenib and lenvatinib efficacy in terms of progression-free survival and, perhaps, overall survival improvement in patients with RAIR-DTC. Lenvatinib performance in RWDs appeared somehow lower than in randomized clinical trials (RCT), probably because the decision to start treatment in 'real life' was made when patients were in worse clinical conditions than in RCTs. Concerning safety, RWD studies corroborated RCT evidence of elevated overall and serious adverse event incidence. Notably, adverse events were manageable in most cases with appropriate treatment or dose reduction/interruption, so that the need for definitive withdrawal was limited. The suitability of multikinase inhibitors (MKI) as salvage therapy in RAIR-DTCs was also confirmed by RWD experience, at least for lenvatinib in the second-line setting. SUMMARY: RWD analysis has corroborated RCT results in terms of MKI efficacy for both first-line and salvage treatment in patients with RAIR-DTC. The safety profiles emerging from RWDs seem to justify the caution recommended by most scientific guidelines.

High dose of radioactive iodine per se has no effect on glucose metabolism in thyroidectomized rats.

PURPOSE: Thyroid concentrates radioactive iodine by sodium-iodide symporter; this is used for treating hyperthyroidism and thyroid cancer. Pancreas expresses NIS and radioactive iodine uptake may damage pancreatic beta-cells and predispose patients to type 2 diabetes. The aim of this study was to determine whether radioactive iodine is associated with glucose metabolism in thyroidectomized rats. METHODS: Forty male Wistar rats were divided into four groups (n = 10/each); control, thyroidectomized, thyroidectomized-treated with 131-I (TX+I), and thyroidectomized-treated with 131-I and L-thyroxine (TX+I+T4). At the end of study, serum fasting glucose, insulin, thyroid-stimulating hormone, and free tetraiodothyronine were measured, intraperitoneal glucose tolerance test was performed, and homeostasis model assessment-insulin resistance was calculated. In in vitro experiments, glucose-stimulated insulin secretion from pancreatic islets and sodium-iodide symporter mRNA expression in thyroid and islets were determined. RESULTS: Compared to control group, free tetraiodothyronine was lower by 41 and 77% and thyroid-stimulating hormone was higher by 36 and 126% in thyroidectomized and TX+I groups, respectively. Compared to controls, rats in TX+I group had glucose intolerance as assessed using the area under curve of intraperitoneal glucose tolerance test (12,376 ± 542 vs. 20,769 ± 1070, P < 0.001) and L-thyroxine replacement therapy restored the value (14,286 ± 328.24) to near normal. Fasting insulin and homeostasis model assessment-insulin resistance were comparable in all groups, however fasting glucose was higher in TX+I group. In in vitro experiments, glucose-stimulated insulin secretion from islets did not differ between groups. CONCLUSION: Radioactive iodine therapy per se had no effect on glucose metabolism, just intensified thyroid hormone deficiency and the alterations on glucose metabolism in thyroidectomized rats. L-thyroxine therapy restored the glucose intolerance observed in radioactive iodine-treated thyroidectomized rats.

Characterization of recombinant human bone morphogenetic protein-2 delivery from injectable hyaluronan-based hydrogels by means of 125I-radiolabelling.

This study presents a thorough in vitro and in vivo characterization of the delivery of bone morphogenetic protein 2 (BMP-2) from a hyaluronan-based hydrogel system. The in vitro release of BMP-2 from similar hydrogels has previously been studied by enzyme-linked immunosorbent assay (ELISA), by which only a fraction of the loaded protein is detected. In the current study, (125) I radiolabelling was used instead to monitor BMP-2 in vitro and in vivo. To minimize protein loss during handling, (125) I-BMP-2 adsorption to different tubes was studied at different times and temperatures. The data showed that Protein LoBind tubes exhibited the lowest protein affinity. Furthermore, a biphasic release profile of biologically active BMP-2 was observed both in vitro and in vivo, with the initial fast phase during the first week, followed by a slower release during the remaining 3 weeks. The initial fast-release phase corresponded to the early bone formation observed after 8 days in an ectopic model in rats. Bone volume and mineral content increased until day 14, after which a decrease in bone volume was observed, possibly due to resorption in response to decreased amounts of released BMP-2. Overall, the results suggested that cautious protein handling and a reliable quantification technique are essential factors for successful design of a BMP-2 delivery system.

Long-term outcome after radioiodine therapy with adjuvant rhTSH treatment: comparison between patients with non-toxic and pre-toxic large multinodular goitre.

In multinodular goitre (MNG), low radioiodine (RAI) activity after recombinant human (rh) TSH is able to reduce thyroid volume (TV) and improve symptoms. Our aim was to evaluate the long-term outcome of RAI after rhTSH treatment in patients who were divided according to their baseline TSH levels. Eighteen patients (69.2 ± 6.1 year) presented non-toxic (TSH >0.3 mIU/l) MNG (TV: 61.0 ± 3.8 ml; group 1), while 13 patients (74.1 ± 7.9 year) had non-autoimmune pre-toxic (TSH <0.3 mIU/l) MNG (TV: 82.6 ± 14.4 ml; group 2). TSH, thyroid hormones, TV (by ultrasonography), body mass index (BMI), symptoms and quality of life (QoL) were evaluated. Treatment induced short-term thyrotoxicosis in both groups, but this was slightly more marked in group 2 than in group 1. The number and severity of adverse events were similar. The follow-up period was 55.3 ± 4.1 months in group 1 and 57.2 ± 5.1 months in group 2. The final TV reduction was similar in groups 1 (63.4 ± 3.6%) and 2 (57.2 ± 4.6%) and TV reduction positively correlated only with initial TV. At the last examination, 14 group-1 subjects were on L-T4 therapy, while 2 group-2 subjects were on methimazole. An increase in BMI was noted only in group 2. MNG-related symptoms were significantly reduced in both groups. Symptoms related to sub-clinical hyperthyroidism improved in group 2, while no significant changes in QoL were noted in either group. This study confirms the effectiveness of rhTSH adjuvant treatment in reducing TV after low RAI activities, irrespective of baseline thyroid status. TSH levels <0.3 mIU/l proved to be predictive of a more severe thyrotoxic phase after rhTSH and RAI, while initial TSH levels >0.3 mIU/l were more frequently followed by a need for L-T4 therapy. Compressive symptoms improved in the majority of subjects.

Cytotoxic and mutagenic effects of iodine-131 and radioprotection of acerola (Malpighia glabra L.) and beta-carotene in vitro.

The radioisotope iodine-131 [(131)I] can damage DNA. One way to prevent this is to increase the amount of antioxidants via dietary consumption. The goal of this study was to evaluate the radioprotective effect of fresh acerola pulp and synthetic beta-carotene in Rattus norvegicus hepatoma cells (HTC) in response to [(131)I] exposure in vitro. Cellular DNA damage was subsequently assessed using a cytokinesis block micronucleus assay. The mutagenic and cytotoxic activities of doses of [(131)I] (0.1, 0.5, 1, 5, and 10 µCi), acerola (0.025, 0.125, and 0.25 g acerola pulp/mL), and beta-carotene (0.2, 1, and 2 µM) were evaluated. Radioprotective tests were performed by simultaneous treatment with acerola (0.25 g/mL) plus [(131)I] (10 µCi) and beta-carotene (0.2 µM) plus [(131)I] (10 µCi). Acerola, beta-carotene, and low concentrations of [(131)I] did not induce micronucleus formation in HTC cells; in contrast, high concentrations of [(131)I] (10 µCi) were mutagenic and induced DNA damage. Moreover, neither acerola nor beta-carotene treatment was cytotoxic. However, acerola reduced the percentage of [(131)I]-induced damage, although beta-carotene did not show a similar effect. Thus, our results suggest that acerola diet supplementation may benefit patients who are exposed to [(131)I] during thyroid diagnostics and therapy.

Radioprotective effect of Ocimum sanctum and amifostine on the salivary gland of rats after therapeutic radioiodine exposure.

The current study investigated the radioprotective effect of Ocimum sanctum on the salivary gland of rats administered radioiodine ((131)I) and compared its efficacy with a known radioprotectant, amifostine. The experimental rats were divided in four groups and sacrificed in three different batches at 1, 3, and 6 months of time interval after 18.5 MBq/100g (i.p.) (131)I exposure. Six months duration batch received (131)I exposure twice with the gap of 3 months. Two groups of experimental rats were presupplemented with O. sanctum (40 mg/kg for 5 days, orally) and amifostine (200 mg/kg, s.c) before (131)I exposure separately. Increased Technetium-99m-pertechnetate ((99m)TcO(4)(-)) uptake at 30 minutes post injection in salivary glands of only (131)I exposed rats may imply delay in clearance at 6 months of exposure in comparison to their counterparts sacrificed at 1 month. Parotid gland histology showed atrophy with lipomatosis in only (131)I exposed rats at 3 and 6 months of duration. O. sanctum and amifostine presupplemented and subsequently exposed to (131)I rats at 3 and 6 months duration exhibited comparable histopathology with controls. Our study indicates possible radioprotective effect of O. sanctum and amifostine against high-dose (131)I exposure.

Clinical application of CT-guided (125)I seed interstitial implantation for local recurrent rectal carcinoma.

PURPOSE: The present study aimed to explore the safety profile and clinical efficacy of CT-guided radioactive seed implantation in treating local recurrent rectal carcinoma. MATERIALS AND METHODS: CT-guided ¹²5I seed implantation was carried out in 20 patients with locally recurrent rectal carcinoma. 14 of the 20 patient had prior adjuvant external-beam radiation therapy (EBRT). The treatment planning system (TPS) was used preoperatively to reconstruct three dimensional images of the tumor and to calculate the estimated seed number and distribution. The median matched peripheral dose (MPD) was 120 Gy (range, 100-160 Gy). RESULTS: Of the 20 patients, 12 were male, 8 were female, and ages ranged from 38 to 78, with a median age of 62. Duration of follow-up was 3-34 months. The response rate of pain relief was 85% (17/20). Repeat CT scan 2 months following the procedure revealed complete response (CR) of the tumor in 2 patients, partial response (PR) in 13 patients, stable disease (SD) in 3 patients, and progressive disease (PD) in 2 patients. 75% of patients had either CR or PR. Median survival time was 18.8 months (95% CI: 3.5-22.4 months). 1 and 2 year survival rates were 75% and 25%, respectively. 4 patients died of recurrent tumor; 4 patients died of distant metastases; 9 patients died of recurrent tumor and distant metastases. 3 patients survived after 2 year follow up. Two patients were found to have mild hematochezia, which was reversible with symptomatic management. CONCLUSION: CT-guided ¹²5I seed implantation appeared to be a safe, useful and less complicated interventional treatment option for local recurrent rectal carcinoma.

(124)I-huA33 antibody PET of colorectal cancer.

UNLABELLED: Humanized A33 (huA33) is a promising monoclonal antibody that recognizes A33 antigen, which is present in more than 95% of colorectal cancers and in normal bowel. In this study, we took advantage of quantitative PET to evaluate (124)I huA33 targeting, biodistribution, and safety in patients with colorectal cancer. We also determined the biodistribution of (124)I-huA33 when a large dose of human intravenous IgG (IVIG) was administered to manipulate the Fc receptor or when (124)I-huA33 was given via hepatic arterial infusion (HAI). METHODS: We studied 25 patients with primary or metastatic colorectal cancer; 19 patients had surgical exploration or resection. Patients received a median of 343 MBq (44.4-396 MBq) and 10 mg of (124)I-huA33. Nineteen patients received the antibody intravenously and 6 patients via HAI, and 5 patients also received IVIG. RESULTS: Ten of 12 primary tumors were visualized in 11 patients. The median concentration in primary colon tumors was 0.016% injected dose per gram, compared with 0.004% in normal colon. The PET-based median ratio of hepatic tumor uptake to normal-liver uptake was 3.9 (range, 1.8-22.2). Quantitation using PET, compared with well counting of serum and tissue, showed little difference. Prominent uptake in bowel hindered tumor identification in some patients. Pharmacokinetics showed that patients receiving IVIG had a significantly shorter serum half-time (41.6 ± 14.0 h) than those without (65.2 ± 9.8 h). There were no differences in clearance rates among the intravenous group, IVIG group, and HAI group, nor was there any difference in serum area under the curve, maximum serum concentration, or volume of distribution. Weak titers of human-antihuman antibodies were observed in 6 of 25 patients. No acute side effects or significant toxicities were associated with huA33. CONCLUSION: Good localization of (124)I-huA33 in colorectal cancer with no significant toxicity has been observed. PET-derived (124)I concentrations agreed well with those obtained by well counting of surgically resected tissue and blood, confirming the quantitative accuracy of (124)I-huA33 PET. The HAI route had no advantage over the intravenous route. No clinically significant changes in blood clearance were induced by IVIG.

Pulmonary aspergilloma mimicking metastasis from papillary thyroid cancer.

BACKGROUND: Whole-body scans (WBSs) based on diagnostic or therapeutic doses of I-131 can visualize metastatic lesions in thyroid cancer patients who have undergone total thyroidectomy. However, a variety of unusual lesions may cause false-positive results, and therefore, careful evaluation of abnormal scans is imperative to avoid unnecessary surgical removal or high-dose radioiodine treatment. Here, we report a patient with pulmonary aspergilloma mimicking metastasis of thyroid cancer on WBS. SUMMARY: A 53-year-old woman with papillary thyroid cancer stage III (T1N1aM0) who had undergone total thyroidectomy and 150 mCi of radioiodine treatment for remnant ablation was found to have focal intense radioiodine accumulation in the left lung field by WBS, suggestive of pulmonary metastasis, at 5 days after I-131 administration. Whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and Tc-99m methoxyisobutyl isonitrile scans showed no remarkable tracer accumulation at the pulmonary nodule. An enhanced chest CT scan demonstrated a nonenhancing pulmonary nodule with an air-crescent sign suggestive of pulmonary fungus ball. A subsequent blood test for precipitating antibodies to Aspergillus antigens produced a result of 29.9 U/mL (reference range: 0-8 U/mL). The patient was clinically diagnosed as having pulmonary aspergilloma based on serologic test and radiologic imaging results. CONCLUSION: Extreme caution should be exercised when interpreting abnormal radioiodine WBS findings when the serum thyroglobulin is normal and imaging characteristics indicate a benign condition. Pulmonary aspergilloma is a cause of a false-positive lesion when radioiodine WBSs are performed.

Disease-related death in patients who were considered free of macroscopic disease after initial treatment of well-differentiated thyroid carcinoma.

BACKGROUND: Death from well-differentiated thyroid cancer (WDTC) is rare, and over the past century there has been a trend away from local recurrence as the primary cause of death. The objective of our study was to report the cause of death from thyroid cancer in patients with WDTC treated with curative intent with surgery ± adjuvant radioactive iodine. METHODS: An institutional database of 1811 patients with WDTC treated surgically for WDTC between 1986 and 2005 was analyzed and identified 165 (9.4%) who had died. Case records were studied to determine the cause of death in each patient. RESULTS: Of the 165 deaths, 17 (10%) patients were confirmed to have died of thyroid cancer and 6 (4%) died of an unknown cause but had thyroid cancer present at the time of last follow-up. The remaining 142 (86%) died from other causes and were considered free of thyroid cancer at their last follow-up. We therefore identified only 23 cause-specific deaths from the entire cohort (1.3%). Of the 17 patients known to have died of thyroid cancer, all had distant recurrence. Ninety-four percent had pulmonary metastases. Of these, 47% also had bony metastasis at the time of death. Two patients had recurrent disease in the neck at the time of death, but both also had distant disease. Of the six patients (4%) who died of unknown causes but had thyroid cancer at last follow-up, four (67%) had distant disease alone, one (17%) had local and regional recurrence, and one had local and distant recurrence at last follow-up. CONCLUSION: After successful resection of WDTC, we report a low disease-specific death rate (1.3%). In contrast to earlier reports, death caused by central compartment disease in this recent series is very rare, with metastatic disease accounting for almost all fatalities.

The direct biologic effects of radioactive 125I seeds on pancreatic cancer cells PANC-1, at continuous low-dose rates.

The relative biologic effectiveness of model 6711 125I seeds (Ningbo Junan Pharmaceutical Technology Company,Ningbo, China) and their effects on growth, cell cycle, and apoptosis in human pancreatic cancer cell line PANC-1 were examined in the present study. PANC-1 cells were exposed to the absorbed doses of 1, 2, 4, 6, 8, and 10 Gyeither with 125I seeds (initial dose rate, 2.59 cGy=h) or with 60Co g-ray irradiation (dose rate, 221 cGy=min),respectively. Significantly greater numbers of apoptotic PANC-1 cells were detected following the continuouslow-dose-rate (CLDR) irradiation of 125I seeds, compared with cells irradiated with identical doses of 60Co g-ray. The D(0) for 60Co g-ray and 125I seed irradiation were 2.30 and 1.66, respectively. The survival fraction after 125Iseed irradiation was significantly lower than that of 60Co g-ray, with a relative biologic effectiveness of 1.39.PANC-1 cells were dose dependently arrested in the S-phase by 60Co g-rays and in the G2=M phase by 125I seeds,24 hour after irradiation. CLDR irradiation by 125I seeds was more effective in inducing cell apoptosis in PANC-1cells than acute high-dose-rate 60Co g irradiation. Interestingly, CLDR irradiation by 125I seeds can cause PANC-1cell-cycle arrest at the G2=M phase and induce apoptosis, which may be an important mechanism underlying 125Iseed-induced PANC-1 cell inhibition.

A simple and safe method for 131I radiolabeling of rituximab for myeloablative high-dose radioimmunotherapy.

The aim of this study was to develop a safe and simple radiolabeling and purification procedure for high-dose (131)I-rituximab for treatment of patients with non-Hodgkin's lymphoma. As the starting point, the conventional Iodogen-coated vial method was applied. After the iodogen-coated monoclonal antibody (mAb) method, a labeling method involving much lower amounts of iodogen was assessed. Subsequently, (131)I-rituximab was purified with a tangential flow filtration system. Quality control of the final product was performed by using size-exclusion chromatography with ultraviolet detection and by instant high-performance thin-layer chromatography. Immunoreactivity was determined by using a cell-binding assay. During the labeling procedure, radiation exposure was monitored. The coated vial method resulted in a low radiation exposure, but immunoreactivity was highly compromised (37%). Also, formation of aggregates was observed. The maximal observed effective dose was 18 microSv, finger thermoluminescence dosemeters revealed a hand-dose measurement of 0.8 mSv. The second method resulted in an immunoreactivity of 70%. Radiochemical purity was >97% after purification. The maximal measured effective dose was 31 microSv, and detected exposure to the hands was 1.9 mSv. We have developed a simple labeling technique for the preparation of high-dose (131)I-rituximab. The method offers a high purity and retained immunoreactivity with minimal radiation exposure for involved personnel.

The impact of thyroid cancer and post-surgical radioactive iodine treatment on the lives of thyroid cancer survivors: a qualitative study.

BACKGROUND: Adjuvant treatment with radioactive iodine (RAI) is often considered in the treatment of well-differentiated thyroid carcinoma (WDTC). We explored the recollections of thyroid cancer survivors on the diagnosis of WDTC, adjuvant radioactive iodine (RAI) treatment, and decision-making related to RAI treatment. Participants provided recommendations for healthcare providers on counseling future patients on adjuvant RAI treatment. METHODS: We conducted three focus group sessions, including WDTC survivors recruited from two Canadian academic hospitals. Participants had a prior history of WDTC that was completely resected at primary surgery and had been offered adjuvant RAI treatment. Open-ended questions were used to generate discussion in the groups. Saturation of major themes was achieved among the groups. FINDINGS: There were 16 participants in the study, twelve of whom were women (75%). All but one participant had received RAI treatment (94%). Participants reported that a thyroid cancer diagnosis was life-changing, resulting in feelings of fear and uncertainty. Some participants felt dismissed as not having a serious disease. Some participants reported receiving conflicting messages from healthcare providers on the appropriateness of adjuvant RAI treatment or insufficient information. If RAI-related side effects occurred, their presence was not legitimized by some healthcare providers. CONCLUSIONS: The diagnosis and treatment of thyroid cancer significantly impacts the lives of survivors. Fear and uncertainty related to a cancer diagnosis, feelings of the diagnosis being dismissed as not serious, conflicting messages about adjuvant RAI treatment, and treatment-related side effects, have been raised as important concerns by thyroid cancer survivors.

Dosimetric evaluation and therapeutic response to internal radiation therapy of hepatocarcinomas using iodine-131-labelled lipiodol.

OBJECTIVE: Vectorized internal radiation therapy using lipiodol-labelled with iodine-131 (131 I-lipiodol) is an effective treatment for inoperable hepatocellular carcinomas. However, few dosimetric data are available based on this approach. We have developed a dosimetric protocol based on scintiscan imaging and that is designed to calculate the tumoural absorbed dose during the treatment of hepatocarcinoma by 131 I-lipiodol. METHODS: This concept was developed on a gamma-camera coupled to a computed tomography scanner. It integrates corrections for attenuation phenomena, scattering and dead time. The tumoural absorbed dose calculation was carried out according to the Medical Internal Radiation Dose Committee formalism. This protocol was applied to a series of 41 patients in the framework of a retrospective study. RESULTS: The mean tumoural absorbed dose with the first treatment is 248 Gy (+/-176), as opposed to 152 Gy (+/-122) during the second. We highlighted a correlation between the tumoural absorbed dose, calculated in tomographic mode, and the morphological response to the first treatment (P=0.0071). Moreover, a tumoural absorbed dose of 280 Gy seems to be an effective absorbed dose threshold in our population. Above this absorbed dose, 84% of the patients are responders after the first treatment, whereas no responses are recorded below this threshold. CONCLUSION: These results are promising because, for the first time, they allow us to predict the effectiveness of a treatment by 131 I-lipiodol. They are required to be validated on a broader exploratory trial, including a dosimetric study of the critical organs, so an individualized dosimetry can be defined for each patient.

131I induced hematological alterations in rat blood: protection by zinc.

The present study was planned to determine the potential of zinc in attenuating the toxicity induced by 131I in rat blood. Female wistar rats were segregated into four main groups. Animals in Group I served as normal controls; Group II animals were administered a dose of 3.7 Mbq of 131I (carrier free) intraperitoneally, Group III was supplemented with Zinc in the form of ZnSo4.7H2O (227 mg/l drinking water), and Group IV was given a combined treatment of Zinc as well as 131I, in a similar way as was given to Groups IV and II animals, respectively. The effects of different treatments were studied on various parameters in rat blood including hemoglobin (Hb) levels, % hematocrit, zinc protoporphyrins (ZPP), activities of enzymes which included aminolevulinic acid dehydratase (delta-ALAD) and Na+ K+ ATPase and uptake of 65Zn in blood. The study revealed an increase in the levels of hemoglobin, % hematocrit, activities of delta-ALAD, Na+ K+ ATPase and uptake of 65Zn, 7 days after the 131I treatment. On the contrary, the levels of ZPP were found to be significantly decreased after 131I treatment. However, zinc treatment to 131I-treated animals significantly attenuated the various biochemical and hematological indices. Moreover, zinc treatment to the 131I-treated animals could significantly decrease the uptake of 65Zn, which was increased after 131I treatment. Based upon these data, the present study suggests that zinc has the potential to attenuate 131I induced toxicity by restoring the altered hematological indices and biochemical changes.

Docetaxel labeled with iodine 131 radionuclide--a possible new anticancer drug? (The pilot study).

The cytotoxic potentials of the lipiodol emulsion with dissolved 131I-docetaxel, the 131I-lipiodol emulsion and non-labeled docetaxel were tested on the HeLa Hep2 cell line during 24 hours. The pilot study confirmed that the radio-labeled docetaxel was significantly more toxic than the radionuclide or docetaxel alone.

Testicular function after radioiodine therapy in patients with thyroid cancer.

Our aim was to assess testicular function in patients treated with high-dose radioiodine. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were determined in 52 men with thyroid carcinoma before and 6, 12, and 18 months after radioiodine therapy (3.7-5.5 GBq (131)I; mean, 4.25 GBq (131)I) (group 1) and were also determined before and 18 months after the last radioiodine therapy in 22 patients who received high cumulative activities (13-27.7 GBq; mean, 20.3 GBq (131)I) (group 2). FSH levels were increased 6 months after therapy in all patients of group 1, while a decline was observed after 12 months, with 37 of 52 (71%) subjects presenting normal values. FSH values returned to normal after 18 months in all patients. In group 2, 12 of 22 (54.5%) patients presented elevated FSH and 8 (66%) of these individuals had oligospermia. Six months after radioiodine, increased LH levels were observed in only 5 of 52 (9.6%) patients of group 1, which returned to normal after 12 months, and in 5 of 22 (22%) of group 2. All patients showed normal testosterone levels. We conclude that 131I therapy may cause impairment of testicular function. A generally transient increase in FSH is highly common but is usually reversed within 18 months. Oligospermia was common (one third) after high cumulative (131)I activities. Becausee we did not perform a spermiogram before therapy, we cannot state that high cumulative (131)I activities cause permanent infertility. We recommend the routine use of sperm banks in the cases of men who still wish to have children and who will undergo therapy with (131)I activities of 14 GBq or more or in the case of patients with pelvic metastases.