131I Radiation Research Articles

Iodine-131 radioembolization boosts the immune activation enhanced by icaritin/resiquimod in hepatocellular carcinoma.

Transarterial radioembolization (TARE) is a recommended locoregional strategy for intermediate hepatocellular carcinoma (HCC), whereas, the effect is insufficient to reverse the immunosuppression tumor microenvironment, and the overall benefits for patients remain to be improved. In this study, a multifunctional microsphere (MS) 131I-ICT/R848-MS is developed to propose an approach combined with TARE, icaritin (ICT) and immune modulator resiquimod (R848). ICT and iodine-131 (131I) radiation can induce immunogenic cell death, which, in combination with R848, will boost dendritic cell (DC) maturation. Decellularized liver model and SPECT/CT imaging revealed high specificity and long retention of microspheres. Radioactive distribution of 131I in tumor on 7 d following 131I-MS injection was over 7 times of that in normal liver tissue (4.26 ± 1.21 % ID/g vs 0.57 ± 0.23 % ID/g). 131I-ICT/R848-MS embolization brought significant immune activation, where the ratio of cytotoxic T lymphocytes to regulatory T cells in tumor sites upregulated from 1.75 ± 0.20 to 24.31 ± 1.79, and DC maturation in lymph nodes increased from 8.90 ± 1.51 % to 34.70 ± 3.12 %. Enhanced anti-tumor efficacy with no relapse was proved in rat orthotopic N1S1 HCC models. These results demonstrated the great potential of this multifunctional embolic agent to treat HCC through transarterial radio-immuno-chemoembolization (TARICE).

Eco-friendly postharvest irradiation strategy with 131I isotope for environmental management of populations of migratory locust, Locusta migratoria

Purpose Irradiation of food is promising for control of pests to minimize postharvest losses of yields and thus improvement of food safety, shelf life of produce. It is a method of choice that induces a series of lethal biochemical and molecular changes culminating into the engagement of a downstream cascade to cause abnormalities in irradiated pests. In this study, the effects of iodine-131 (131I) isotope radiation on the male gonad development of the migratory locust, Locusta migratoria, were evaluated. Materials and methods Newly emerged adult male locusts, less than one-day-old, were divided into two groups, control and irradiated. Locusts in the control group (n = 20 insects) didn’t drink irradiated water and were reared under normal environmental conditions for one week. Locusts in the irradiated group (n = 20 insects) were exposed to irradiated water at a dose of 30 mCi and they were subsequently observed until they drank the whole quantity. Results At the end of the experiment, scanning and electron microscopic examination of testes obtained from irradiated locusts revealed several major abnormalities, including malformed nuclei of spermatozoa, irregular plasma membranes, shrinkage of testicular follicles, vacuolated cytoplasm, disintegrated nebenkern and agglutinations of spermatids. Flow cytometry analysis revealed that 131I radiation induced both early and late apoptosis, but not necrosis, in testicular tissues. Testes of irradiated insects also exhibited a burst in reactive oxygen species (ROS), as indicated by significant elevation in amounts of malondialdehyde (MDA), a marker for peroxidation of lipids. In contrast, irradiation coincided with significant reductions in activities of enzymatic antioxidant biomarkers. Relative to controls, a three-fold upregulation of expression of mRNA of heat shock protein, Hsp90, was observed in testicular tissue of irradiated locusts. 131I-irradiated insects exhibited genotoxicity, as indicated by significant increases in various indicators of DNA damage by the comet assay, including tail length (7.80 ± 0.80 µm; p < .01), olive tail moment (40.37 ± 8.08; p < .01) and tail DNA intensity % (5.1 ± 0.51; p < .01), in testicular cells compared to the controls. Conclusion This is the first report on elucidation of I131-irradiation-mediated histopathological, biochemical and molecular mechanisms in gonads of male L. migratoria. Herein, the findings underscore the utility of 131I radiation as an eco-friendly postharvest strategy for management of insect pests and in particular for control of populations of L. migratoria.

Current Status of TRIPOLI-4® Monte Carlo Radiation Transport Code on Adult and Pediatric Computational Phantoms for Radiation Dosimetry Study

TRIPOLI-4® is a general-purpose Monte Carlo radiation transport code developed by the Service d’Études des Réacteurs et de Mathématiques Appliquées at CEA-Saclay. It uses continuous-energy nuclear data to simulate neutron, photon, electron, and positron transport in fields like radiation shielding, reactor physics, and nuclear criticality safety. To study radiation protection dosimetry in human tissues and organs, male and female adult computational phantoms from the Medical Internal Radiation Dose–Oak Ridge National Laboratory phantoms family and the International Commission on Radiological Protection (ICRP) publication 110 were recently modeled and calculated using the geometry options of TRIPOLI-4. To easily use the ICRP 110 voxel-based phantoms in different exposure scenarios, a newly developed phantom option is available in TRIPOLI-4 and its display tool T4G. This new phantom option is helpful for modeling one or more phantoms and for improving calculation performance in real irradiation environments. The 2020 published pediatric computational reference phantoms are accessible from ICRP publication 143. Male and female pediatric phantoms are also verified with the new T4G tool and TRIPOLI-4 code. This paper reports on recent works using TRIPOLI-4 on adult and pediatric computational phantoms. The modeling methods of stylized and voxel-based phantoms, the graphic displays of modeled phantoms with T4G, and the verification procedures for single-phantom and two-phantom application cases are presented. Validation for external and internal dosimetry calculations has been performed. Calculation results on organ dose S values for nuclear medicine applications are presented for single female and single male voxel phantoms using 131I and 177Lu radiation sources. Effective dose calculations for two-phantom cases using 99mTc and 18F sources are compared with traditional H*(10) calculations from nuclear medicine patient to patient caregiver.

Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry.

Background: Delivery of radiotherapeutic dose to recurrent head and neck cancer (HNC) is primarily limited by locoregional toxicity in conventional radiotherapy. As such, HNC patients stand to benefit from the conformal targeting of primary and remnant disease achievable with radiopharmaceutical therapies. In this study, the authors investigated the tumor targeting capacity of 131I-CLR1404 (iopofosine I-131) in various HNC xenograft mouse models and the impact of partial volume correction (PVC) on theranostic dosimetry based on 124I-CLR1404 (CLR 124) positron emission tomography (PET)/computed tomography (CT) imaging. Methods: Mice bearing flank tumor xenograft models of HNC (six murine cell line and six human patient derived) were intravenously administered 6.5-9.1 MBq of CLR 124 and imaged five times over the course of 6 d using microPET/CT. In vivo tumor uptake of CLR 124 was assessed and PVC for 124I was applied using a novel preclinical phantom. Using subject-specific theranostic dosimetry estimations for iopofosine I-131 based on CLR 124 imaging, a discrete radiation dose escalation study (2, 4, 6, and 8 Gy) was performed to evaluate tumor growth response to iopofosine I-131 relative to a single fraction of external beam radiation therapy (6 Gy). Results: PET imaging demonstrated consistent tumor selective uptake and retention of CLR 124 across all HNC xenograft models. Peak uptake of 4.4% ± 0.8% and 4.2% ± 0.4% was observed in squamous cell carcinoma-22B and UW-13, respectively. PVC application increased uptake measures by 47%-188% and reduced absolute differences between in vivo and ex vivo uptake measurements from 3.3% to 1.0 percent injected activity per gram. Tumor dosimetry averaged over all HNC models was 0.85 ± 0.27 Gy/MBq (1.58 ± 0.46 Gy/MBq with PVC). Therapeutic iopofosine I-131 studies demonstrated a variable, but linear relationship between iopofosine I-131 radiation dose and tumor growth delay (p < 0.05). Conclusions: Iopofosine I-131 demonstrated tumoricidal capacity in preclinical HNC tumor models and the theranostic pairing with CLR 124 presents a promising new treatment approach for personalizing administration of iopofosine I-131.

Optical diagnostic imaging and therapy for thyroid cancer.

Thyroid cancer, as one of the most common endocrine cancers, has seen a surge in incidence in recent years. This is most likely due to the lack of specificity and accuracy of its traditional diagnostic modalities, leading to the overdiagnosis of thyroid nodules. Although there are several treatment options available, they are limited to surgery and 131I radiation therapy that come with significant side effects and hence cannot meet the treatment needs of anaplastic thyroid carcinoma with very high malignancy. Optical imaging that utilizes optical absorption, refraction and scattering properties, not only observes the structure and function of cells, tissues, organs, or even the whole organism to assist in diagnosis, but can also be used to perform optical therapy to achieve targeted non-invasive and precise treatment of thyroid cancer. These applications of screening, diagnosis, and treatment, lend to optical imaging's promising potential within the realm of thyroid cancer surgical navigation. Over the past decade, research on optical imaging in the diagnosis and treatment of thyroid cancer has been growing year by year, but no comprehensive review on this topic has been published. Here, we review key advances in the application of optical imaging in the diagnosis and treatment of thyroid cancer and discuss the challenges and potential for clinical translation of this technology.

Influence of Dehydroxymethylepoxyquinomicin on Radiosensitivity of Thyroid Carcinoma TPC-1 Cells.

Objective To investigate the influence of dehydroxymethylepoxyquinomicin (DHMEQ), an NF-κB inhibitor, on radiosensitivity of thyroid carcinoma (TC) TPC-1 cells. Methods The isolation of CDl33 positive cells (CD133+ TPC-1) and negative cells (CD133− TPC-1) from TPC-1 cells used immunomagnetic bead sorting. After verification of the toxicity of DHMEQ to cells by MTT and cell cloning assays, the cells were divided into four groups, of which three groups were intervened by DHMEQ, 131I radiation, and DHMEQ +131I radiation, respectively, while the fourth group was used as a control without treatment. Alterations in cell growth, apoptosis, and cell cycle were observed. Results DHMEQ had certain toxic effects on TPC-1 cells, with an IC50 of 38.57 μg/mL (P < 0.05). DHMEQ inhibited CD133+ and CD133- TPC-1 proliferation and their clonogenesis after irradiation. DHMEQ + radiation contributed to a growth inhibition rate and an apoptosis rate higher than either or them alone (P < 0.05), with a more significant effect on CD133− TPC-1 than CD133+ TPC-1 under the same treatment conditions (P < 0.05). Conclusion DHEMQ can increase the radiosensitivity of TC cells to 131I, inhibit tumor cell growth, and promote apoptosis. However, its effect is less significant on CD133+ TPC-1 compared with CD133− TPC-1, which may be related to the stem cell-like properties of CD133+ cells. In the future, the application of DHMEQ in TC 131I radiotherapy will effectively improve the clinical effect of patients.

Analysis of the incidence of thyroid cancer in the population of the Oryol Region

The article presents the results of a study of the oncological morbidity of the population of the Orel region, including thyroid cancer (prostate cancer). After the accident at the Chernobyl nuclear power Plant (Chernobyl NPP), particularly rapid rates of increase in the incidence of breast cancer were detected among the children (at the time of the accident) population. According to experts dealing with the problem of breast cancer, in addition to direct radiation exposure, a significant contribution could be made due to screening (that is, increased detectability as a result of mass examinations using ultrasound diagnostics), the presence of iodine deficiency in these territories, improper iodine prevention after an accident. The purpose is to analyze the problems of the prevalence of cancer in the country; to study the incidence of thyroid cancer in the population of the country and the Orel region and to present an analysis of the incidence of thyroid cancer in the Orel region in comparison with other regions. The materials of the study were generalized official data of annual medical statistics (Forms No., No. 7, 35), in dynamics from 1981 to 2019. The analysis of the incidence of thyroid cancer in the territories exposed to radiation as a result of the Chernobyl accident was carried out. As of 2019, the Orel region was on the 16th place out of 85 possible in the incidence of malignant neoplasms (ZNO). The incidence rate was 546.9 cases per 100 thousand population, which is significantly higher than the incidence rate in the Russian Federation. Over a 38-year period (from 1981 to 2019), the incidence of prostate cancer per 100 thousand population of the Orel region increased 6.5 times. Among the regions affected by the Chernobyl accident, the Orel region also occupies a leading position in terms of the incidence of prostate cancer. The increased incidence of adult breast cancer is associated, apparently, with a change in the conditions of dispensary observation. According to the National Register, the doses of thyroid radiation among the children’s population at the time of the Chernobyl disaster in the Bryansk region reach 300–400 mGr, in the Orel region, the doses of thyroid radiation among the children’s population are significantly less and do not exceed 30 mGr. A retrospective radiological and epidemiological analysis showed that about 30 % of thyroid cancer cases in children in the Bryansk region were caused by ¹³¹I irradiation during the Chernobyl accident. In the Orel region, the role of the radiation factor in the dynamics of the incidence of thyroid cancer in children has not been confirmed. Thus, one of the most significant problems in the radiation-contaminated territories, to which the Orel region belongs, is the steady increase in the number of patients with prostate cancer. At the same time, the main contribution to the increase in indicators was made due to screening (for example, an increased probability of detection due to the use of ultrasound diagnostics for large-scale examinations), and, to a lesser extent, due to direct radiation exposure, iodine deficiency and insufficient prevention after an accident.

Comparison of early forecasts of the incidence of thyroid cancer in residents of the Russian Federation after the Chernobyl accident with observational data

A review of methods for assessing doses in the thyroid gland, predictions of the long-term consequences of its irradiation and the actual incidence of thyroid cancer in residents of four regions of the Russian Federation with the most significant radioactive fallout after the Chernobyl accident are presented. The method for assessing doses in the thyroid gland is based on the results of monitoring in May-June 1986 of radioiodine in the environment, food and in the body of residents. Thyroid doses in the population were used to justify medical and social protection measures, as well as epidemiological studies. In addition, the authorities needed forecasts of the possible morbidity of the population in order to organize adequate medical care. Most of the thyroid cancer cases were predicted among the adult population, which was not confirmed by observations 35 years after the accident. The prognosis of the incidence of thyroid cancer in preschool children differed in different studies due to the use of different coefficients of reducing the biological effectiveness of 131I radiation in the thyroid gland and long-term external and internal irradiation of the whole body with a low dose rate compared to the effect of acute exposure. The increase in the incidence of thyroid cancer among children began five years after the accident at the Chernobyl nuclear power plant. Examples of the dynamics of the incidence for children in the Bryansk region of the Russian Federation are given. The 2018 UNSCEAR Report showed that for 1986-2015, among children and adolescents under 18 years of age on the day of the accident in Belarus, Ukraine and four regions of Russia, more than 19 thousand thyroid cancer cases were detected, of which the share of radiation-induced diseases was estimated at 25%. For four regions of Russia, this amounts to 460 cases with a range of possible estimates from 130 to 900 cases. The highest morbidity was manifested among younger children exposed at the age of 0-4 years. In older children and adolescents, the proportion of radiation-induced diseases has significantly decreased 30 years after the accident. In general, early forecasts of radiation-induced thyroid cancer incidence in children in four regions of the Russian Federation with high levels of radioactive fallout are consistent with the data of subsequent 30-year epidemiological observations within an order of magnitude. With regard to thyroid cancer in adults, such a comparison is difficult, since no radiogenic increase in the incidence has been detected.

Na+/I- symporter expression, function, and regulation in non-thyroidal tissues and impact on thyroid cancer therapy.

For the past 80 years, radioiodine (131I) has been used to ablate thyroid tissue not removed by surgery or to treat differentiated thyroid cancer that has metastasized to other parts of the body. However, the Na+/I- symporter (NIS), which mediates active iodide uptake into thyroid follicular cells, is also expressed in several non-thyroidal tissues. This NIS expression permits 131I accumulation and radiation damage in these non-target tissues, which accounts for the adverse effects of radioiodine therapy. We will review the data regarding the expression, function, and regulation of NIS in non-thyroidal tissues and explain the seemingly paradoxical adverse effects induced by 131I, the self-limited gastrointestinal adverse effects in contrast to the permanent salivary dysfunction that is seen after 131I therapy. We propose that prospective studies are needed to uncover the time-course of pathological processes underlying development and progression or ultimate resolution of 131I-induced salivary ductal obstruction and nasolacrimal duct obstruction. Finally, preventive measures and early therapeutic interventions that can be applied potentially to eliminate or alleviate long-term radioiodine adverse effects will be discussed.

Simultaneous measurements of single gamma ray of 131I and annihilation radiation of 18F with Compton PET hybrid camera

In internal 131I therapy for thyroid cancer, a decision to continue treatment is made by comparing 131I scintigraphy and [18F]FDG-PET. However, with current SPECT and PET systems, simultaneous imaging of diagnostic PET nuclides and therapeutic 131I nuclides has not been achieved so far. Therefore, we demonstrated that the recently developed Compton PET hybrid camera with Ce:Gd3(Al,Ga)5O12 (GAGG)- Silicon Photomultiplier(SiPM) scintillation detectors can be used to simultaneously image 131I Compton image and 18F PET image.

Feasibility of Bone Marrow Mesenchymal Stem Cell-Mediated Synthetic Radiosensitive Promoter-Combined Sodium Iodide Symporter for Radiogenetic Ovarian Cancer Therapy.

Ovarian cancer is the most lethal gynecological cancer, most patients relapse within 12-24 months, and eventually die, especially platinum-resistant patients. Gene therapy has been one of the most potential methods for tumor treatment. Bone marrow mesenchymal stem cells (BMSCs) have been used for systemic delivery of therapeutic genes to solid tumors. Sodium iodide symporter (NIS) is an intrinsic membrane glycoprotein and can concentrate 131I, which is important for radionuclide therapy and nuclear medicine imaging in recent years. However, the rapid iodine efflux has become a bottleneck for NIS-mediated radionuclide gene therapy. Our previous studies found that the early growth response-1 (Egr1) promoter containing CC(A/T)6GG (CArG) elements had an 131I radiation-positive feedback effect on the NIS gene. Other research showed the synthesized Egr1 promoter containing four CArG elements, E4, was nearly three times as sensitive as the Egr1 promoter. In our study, BMSC-E4-NIS was engineered to express NIS under the control of E4 promoter using lentivirial vectors. After BMSC-E4-NIS implantation, no tumors were seen in BALB/c nude mice and BMSC-E4-NIS did not promote the growth of SKOV3 tumor. BMSCs migrated toward ovarian cancer samples in chemotaxis assays and to ovarian tumors in mice. Using micro-single-photon emission computed tomography/computed tomography (SPECT/CT) imaging, we found that E4 promoter produced a notable increase in 125I uptake after 131I irradiation, the radionuclide uptake is almost three and six times more than Egr1 and cytomegalovirus (CMV) promoters. These studies confirmed the feasibility of using BMSCs as carriers for lentivirus-mediated E4-NIS gene therapy for ovarian cancer. Further research on BMSC-E4-NIS gene therapy for ovarian cancer in vivo will also be carried on, and if successful, this might provide a new adjuvant therapeutical option for platinum-resistant ovarian cancer patients and provide a new method for dynamic evaluation of curative effect.

Clinical and Sialographic Imaging Features of 131I Radiation-induced Submandibular Gland Sialadenitis

131I radiation-induced sialadenitis is the most frequent complication of 131I treatment for papillary thyroid carcinoma, but little is known about 131I radiation-induced submandibular gland sialadenitis. The purpose of this study was to compare and contrast the clinical and sialographic imaging features of 131I radiation-induced submandibular gland sialadenitis to 131I radiation-induced parotitis. This retrospective cross-sectional study included patients with 131I radiation-induced submandibular gland sialadenitis and parotitis. Clinical records and sialographic image features were evaluated. The predictor variables included age at the time of diagnosis, gender, course of the disease, site of symptoms, and sialographic image grades. The outcome variable was the location of sialadenitis. A student t-test was conducted to analyze the associations between predictor variables and the outcome. The sample was composed of 4 patients with submandibular gland sialadenitis (100% female), 28 with parotitis (85.7% female), and 1 with submandibular gland sialadenitis and parotitis (P<.05). The occurrence of bilateral glands dysfunction was less often in submandibular glands (SMG: 1/4; PG: 19/28). The age and course of disease were not different between submandibular gland sialadenitis and parotitis (Age, SMG: 46.00±13.59years; PG: 50.04±10.71years, P>.05; Course of the disease, SMG: 11.00±16.69months; PG: 6.96±11.18months, P>.05). Radiographically, 7 of 16 patients with parotitis were identified as grade 2 and 9 patients as grade 3. In 3 patients with submandibular gland sialadenitis, 1patient was identified as grade 2 and 2 patients as grade 3. The postoperative pathological results showed that the proliferation of glandular tissue from the hilum of the submandibular gland caused duct stenosis. The results suggest 131I radiation-induced submandibular gland sialadenitis has a lower incidence compared with parotitis and 131I radiation-induced submandibular gland sialadenitis might be related to duct stenosis caused by proliferative glandular tissue after 131I radiation treatment.

NES1/KLK10 and hNIS gene therapy enhanced iodine-131 internal radiation in PC3 proliferation inhibition.

NES1 gene is thought to be a tumor-suppressor gene. Our previous study found that overexpression of NES1 gene in PC3 cell line could slow down the tumor proliferation rate, associated with a mild decrease in BCL-2 expression. The BCL-2 decrease could increase the sensitivity of radiotherapy to tumors. Thus, we supposed to have an "enhanced firepower" effect by combining overexpressed NES1 gene therapy and 131I radiation therapy uptake by overexpressed hNIS protein. We found a weak endogenous expression of hNIS protein in PC3 cells and demonstrated that the low expression of hNIS protein in PC3 cells might be the reason for the low iodine uptake. By overexpressing hNIS in PC3, the radioactive iodine uptake ability was significantly increased. Results of in vitro and in vivo tumor proliferation experiments and 18F-fluorothymidine (18F-FLT) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging showed that the combined NES1 gene therapy and 131I radiation therapy mediated by overexpressed hNIS protein had the best tumor proliferative inhibition effect. Immunohistochemistry showed an obvious decrease of Ki-67 expression and the lowest BCL-2 expression. These data suggest that via inhibition of BCL-2 expression, overexpressed NES1 might enhance the effect of radiation therapy of 131I uptake in hNIS overexpressed PC3 cells.

Оценка дозы в щитовидной железе крупного рогатого скота с помощью камерной модели метаболизма йода и расчёта транспорта излучений методом Монте-Карло

Purpose: This work aims first to improve the reliability of absorbed dose calculation in critical organs of cattle during internal irradiation immediately after radiation accidents by a) improving the compartmental model of radionuclide metabolism in animal body; b) the use of precision computing technologies for modeling as the domain, and the actual radiation transport. In addition, the aim of the work is to determine the agreed values of the 131I critical dose in the cattle thyroid, leading to serious gland dysfunction and its follow-up destruction.&#x0D; Material and methods: To achieve aforecited goals, comprehensive studies were carried out to specify the parameters of the compartmental model, based on reliable experimental and theoretical data. Voxel technologies were applied for modeling the subject domain (thyroid gland and its environment). Finally, to solve the 131I radiation transport equation, the Monte Carlo code was applied, which takes into account the contribution of gamma and beta radiation source, and the contribution of the entire chain of secondary radiations in the dose calculation, up to the total energy dissipation.&#x0D; Results: As the main theoretical result, it is necessary to emphasize the conversion factor from the 131I activity, distributed uniformly in volume of the thyroid gland, to the average dose rate in the gland (Bq × Gy/s). This factor was calculated for both cows and calves in the selected domain configuration and thyroid morphology. The main practical result is a reliable estimation the lower bound of the absorbed dose in the thyroid, which in a short time leads to its destruction under internal 131I irradiation: ~300 Gy.&#x0D; Conclusion: Usage a compartmental model of the 131I metabolism with biokinetic parameters, received on the basis of reliable experimental data, and precise models of both the subject area and radiation transport for evaluation the dose in the cattle thyroid after the radiation accident allowed to obtain reliable values of the thyroid dose, adducting to its destruction at short notice.

The Molecular Effect of Diagnostic Absorbed Doses from 131I on Papillary Thyroid Cancer Cells In Vitro.

Diagnostic whole-body scan is a standard procedure in patients with thyroid cancer prior to the application of a therapeutic dose of 131I. Unfortunately, administration of the radioisotope in a diagnostic dose may decrease further radioiodine uptake—the phenomenon called “thyroid stunning”. We estimated radiation absorbed dose-dependent changes in genetic material, in particular in the sodium iodide symporter (NIS) gene promoter, and the NIS protein level in a K1 cell line derived from the metastasis of a human papillary thyroid carcinoma exposed to 131I in culture. The different activities applied were calculated to result in absorbed doses of 5, 10 and 20 Gy. Radioiodine did not affect the expression of the NIS gene at the mRNA level, however, we observed significant changes in the NIS protein level in K1 cells. The decrease of the NIS protein level observed in the cells subjected to the lowest absorbed dose was paralleled by a significant increase in 8-oxo-dG concentrations (p < 0.01) and followed by late activation of the DNA repair pathways. Our findings suggest that the impact of 131I radiation on thyroid cells, in the range compared to doses absorbed during diagnostic procedures, is not linear and depends on various factors including the cellular components of thyroid pathology.

Monte Carlo simulation of the RBE of I-131 radiation using DNA damage as biomarker.

In general, a weighting factor of one is applied for low linear energy transfer radiations. However, several studies indicate that relative biological effectiveness (RBE) of low energy photons and electrons is greater than one. The aim of this current study was calculating the RBE of I-131 radiation relative to Co-60 gamma photons in 100 μm spheroid cells using Monte Carlo (MC) simulations. These calculations were compared to experimentally measured results. MCNPX2.6 was used to simulate the I-131 and Co-60 irradiation setups and calculate the secondary electron spectra at energies higher than 1keV with varying oxygen concentrations. The electron spectra at energies lower than 1keV were obtained by extrapolation (down to 10eV). The calculated electron spectra were input into the MCDS micro-dosimetric Monte Carlo code to calculate the DSB induction and related RBE. The calculated RBE of I-131 radiation relative to Co-60 photons, as the reference radiation recommended by the International Commission on Radiation Protection (ICRP), was 1.06, 1.03 and 1.02 for oxygen concentrations of 0, 5 and 100%, respectively. Results of MC simulations indicate the RBE of I-131 is greater than one. This finding, despite a 10% discrepancy with the findings of theprevious in vitro study of one of the authors of this paper, reemphasizes that I-131 radiation induces more severe biological damage than current ICRP recommendations.

Effect of selenium supplementation for protection of salivary glands from iodine-131 radiation damage in patients with differentiated thyroid cancer.

In the current study, we examined whether selenium supplementation during iodine-131 (131I) treatment had a radio-protective effect on salivary glands. Sixteen patients with differentiated thyroid cancer were prospectively enrolled in the study. Patients after total thyroidectomy, before 131I treatment, were divided into two groups; 8 patients in the selenium group and 8 patients in the control group. Patients in the selenium group received 300νg of selenium orally for 10 days, from 3 days before to 6 days after 131I treatment. The control group received a placebo over the same period. To assess salivary gland function, salivary gland scintigraphy was performed before and 6 months after 131I treatment. Serum amylase and whole blood selenium levels were measured before and 2 days and 6 months after 131I treatment. Using salivary gland scintigraphy, maximum uptake ratio (MUR), maximum secretion percentage (MSP), and ejection fraction (EF) of each salivary gland were calculated. Baseline clinical characteristics, baseline amylase and selenium levels, and parameters of baseline salivary gland scintigraphy were not significantly different between selenium and control groups (P>0.05). On a blood test performed 2 days after 131I treatment, the selenium group showed a significantly higher whole blood selenium level (P=0.008) and significantly lower serum amylase level (P=0.009) than the control group. On follow-up salivary gland scintigraphy, the control group showed significantly decreased, MUR of the bilateral parotid and left submandibular glands, MSP of the bilateral parotid and submandibular glands, and EF of the left submandibular glands (P<0.05), while the selenium group only had a significant decrease in MSP of the right submandibular gland and EF of the left submandibular gland (P<0.05). Selenium supplementation during 131I treatment was effective to reduce salivary glands damage by 131I radiation in patients with differentiated thyroid cancer.

Estimating (131)I biokinetics and radiation doses to the red marrow and whole body in thyroid cancer patients: probe detection versus image quantification.

ObjectiveTo compare the probe detection method with the image quantification method when estimating 131I biokinetics and radiation doses to the red marrow and whole body in the treatment of thyroid cancer patients.Materials and MethodsFourteen patients with metastatic thyroid cancer, without metastatic bone involvement, were submitted to therapy planning in order to tailor the therapeutic amount of 131I to each individual. Whole-body scans and probe measurements were performed at 4, 24, 48, 72, and 96 h after 131I administration in order to estimate the effective half-life (Teff) and residence time of 131I in the body.ResultsThe mean values for Teff and residence time, respectively, were 19 ± 9 h and 28 ± 12 h for probe detection, compared with 20 ± 13 h and 29 ± 18 h for image quantification. The average dose to the red marrow and whole body, respectively, was 0.061 ± 0.041 mGy/MBq and 0.073 ± 0.040 mGy/MBq for probe detection, compared with 0.066 ± 0.055 mGy/MBq and 0.078 ± 0.056 mGy/MBq for image quantification. Statistical analysis proved that there were no significant differences between the two methods for estimating the Teff (p = 0.801), residence time (p = 0.801), dose to the red marrow (p = 0.708), and dose to the whole body (p = 0.811), even when we considered an optimized approach for calculating doses only at 4 h and 96 h after 131I administration (p > 0.914).ConclusionThere is full agreement as to the feasibility of using probe detection and image quantification when estimating 131I biokinetics and red-marrow/whole-body doses. However, because the probe detection method is inefficacious in identifying tumor sites and critical organs during radionuclide therapy and therefore liable to skew adjustment of the amount of 131I to be administered to patients under such therapy, it should be used with caution.

131I therapy mediated by sodium/iodide symporter combined with kringle 5 has a synergistic therapeutic effect on glioma.

Glioblastoma (GBM) is the most common and most aggressive primary brain tumor; the prognosis of patients with GBM remains poor. The sodium/iodide symporter (NIS) can be used to absorb several isotopes, such as 131I for nuclear medicine imaging and radionuclide therapy. Previously, we found that the early growth response-1 (Egr1) promoter had an 131I radiation positive feedback effect on the NIS gene. Kringle 5 (K5), a kringle domain of plasminogen, induced endothelial cell apoptosis. We investigated the effect of K5 combined with the 131I radiation positive feedback effect (Egr1-NIS) for treating malignant U87 glioma cells using a lentiviral vector. We successfully constructed a stable U87 glioma cell line, U87-K5-Egr1-NIS. The radio-inducible Egr1 promoter induced an 131I radiation positive feedback effect absorbed by NIS. Mediated by 131I, K5 increased glioma cell apoptosis; 131I radiation also increased endothelial cell sensitivity to K5-induced apoptosis. The combined therapy had a synergistic effect on the antitumor efficacy of glioma treatment, not only increasing tumor cell apoptosis but also significantly inhibiting tumor cell proliferation and reducing capillary density in U87 glioma tissues.

Mechanism of dedifferentiation in differentiated thyroid cancer

131 I-metabolizing genes are markers for differentiation of thyroid carcinoma.The loss or down-regulation of these genes represents progression of dedifferentiation,which results in low 131 I uptake and suggests a poor prognosis.The mechanism of dedifferentiation of DTC is important for treatment.This article reviews the mechanism of dedifferentiation from 131I radiation damage,gene mutation,tumor markers and protein. Key words: Thyroid neoplasms ; Radiotherapy; Iodine radioisotopes ; Genes ; Mutation; Trends