131I Therapy Research Articles

Bone Marrow Mesenchymal Stem Cell-Mediated Radiosensitive Promoter-Combined Sodium Iodide Symporter for the Treatment of Breast Cancer.

To develop genetically engineered bone marrow mesenchymal stem cells (BMSCs) that carries a radiotherapy gene to target triple-negative breast cancer (TNBC) and to evaluate the efficacy of radiation damage within the tumor microenvironment. The early growth response protein1 (Egr1)-human sodium iodide symporter (hNIS) gene was transfected into BMSCs by lentiviral transfection and the expression levels were evaluated by quantitative reverse transcription polymerase chain reaction. Transwell and adipogenesis and osteogenesis assays were performed to determine the targeting properties and adipogenic and osteogenic characteristics of the transgenic stem cells. The uptake of radioiodine and the efflux characteristics of the transgenic stem cells were determined by iodine uptake experiments. 131I-SPECT imaging was used to determine the characteristics of targeting to TNBC and to quantify the iodine uptake of transgenic stem cells in vivo. The effects of 131I treatment on BMSCs were characterized using tumor growth, immune cell infiltration, and tumor invasion endpoints based on immunohistochemistry and flow cytometry analysis of tumor samples. BMSCs-Egr1-hNIS cells abundantly express hNIS after radiation induction and are chemotactically attracted to TNBC tumors. Iodine uptake of BMSCs-Egr1-hNIS gradually increased with increasing induction concentrations and times. When the inductive concentration of 131I was >100 μCi/mL and lasted for 36 h, the rate of iodine uptake in cells increased. In vitro, the radioiodine quickly flowed out from cells within 20 min but in vivo, the rate of radioiodine loss was significantly slower and occurred over 24 h. After 131I therapy, tumor growth was inhibited, white blood cells infiltrated into tumor site and the levels of invasion-related cytokines significantly decreased. BMSCs-Egr1-hNIS-mediated 131I therapy can achieve precisely targeted radiotherapy to inhibit tumor growth, promote immune cell infiltration to the tumor sites, and reduce the invasiveness and metastasis characteristics of tumor cells.

The relationship between genetic characteristics and clinical characteristics and the efficacy of 131I therapy in children and adolescents with locally advanced or metastatic differentiated thyroid cancer

The relationship between genetic characteristics and clinical characteristics and the efficacy of 131I therapy in children and adolescents with locally advanced or metastatic differentiated thyroid cancer

Clinical outcome of 131I therapy in differentiated thyroid cancer patients with suspicious high thyroglobulin concentration

Clinical outcome of 131I therapy in differentiated thyroid cancer patients with suspicious high thyroglobulin concentration

Abstract #1184631: Persistent Azoospermia Following Radioactive Iodine I-131 Therapy for Thyroid Cancer in a Previously Fertile Male

Decreased sperm counts and infertility are known complications following radiation therapy, but are not commonly seen as a side effect of radioactive iodine (RAI) I-131 treatment for thyroid cancer. When present after RAI I-131, these effects are usually transient and typically resolve within one year following treatment. It is rare for a patient to experience persistent azoospermia with commonly used thyroid carcinoma treatment doses, especially in the absence of fertility impairment prior to RAI exposure.

Modified dynamic risk stratification system further predicts individual outcome in patients with intermediate-risk papillary thyroid cancer

ObjectiveWe assessed the contribution of initial treatment response to further refining prediction of individual outcomes in intermediate-risk papillary thyroid cancer (PTC) on the American Thyroid Association (ATA) risk stratification system. Dynamic risk stratification (DRS) as originally proposed by Tuttle et al. in 2010 was modified to also include serum antithyroglobulin antibodies (TgAb) as a surrogate marker of the likelihood of persistent disease, specifically in patients with thyroglobulin assay interference by TgAb. MethodsThree hundred and seventy-three patients with ATA intermediate-risk PTC were enrolled retrospectively upon reviewing medical records. Patients were followed at the National Cancer Institute in Bogota, Colombia after being treated with total thyroidectomy and I-131 therapy between 2009 and 2013. Best response to initial therapy was classified as excellent, indeterminate, biochemically incomplete or structurally incomplete. Final disease status after a median follow-up of 7.1 years was classified as no evidence of disease (NED), indeterminate, or persistent disease (either biochemically or structurally). The rate of recurrence was determined in excellent responders. ResultsExcellent response was achieved by 164 patients (43.9%). At a median follow-up of 42 months, 19 (11.6%) had experienced recurrence. 87.4% of initially excellent responders available at the final checkpoint were NED, compared to 28% of those with biochemically or structurally incomplete response and to 60.2% of all ATA intermediate-risk PTC patients in our cohort. ConclusionsModified DRS further predicted individual outcomes in intermediate-risk PTC, potentially allowing ongoing management to be tailored accordingly.

Clinical experience following implementation of routine SPECT-CT imaging following 131-iodine administration for thyroid cancer.

BackgroundPlanar scintigraphy has long been indicated in patients receiving I-131 therapy for thyroid cancer to determine the anatomic location of metastases. We studied our experience upon implementing additional single-photon emission (SPECT)-CT scanning in these patients.MethodWe performed a retrospective study of consecutive adult patients with newly diagnosed thyroid cancer treated with I-131 between 2011 and 2017. Radiologic findings detected with planar scintigraphy alone vs those identified with SPECT-CT scanning were primary endpoints.ResultIn this study, 212 consecutive patients with thyroid cancer were analyzed in two separate cohorts (107 planar scintigraphy alone and 105 planar scintigraphy with SPECT-CT). The addition of SPECT-CT resulted in more findings, both thyroid-related and incidental. However, we identified only 3 of 21 cases in which SPECT-CT provided an unequivocal additional benefit by changing clinical management beyond planar scintigraphy alone. No difference in the detection of distant metastatic disease or outcome was identified between cohorts.ConclusionSynergistic SPECT-CT imaging in addition to planar nuclear scintigraphy adds limited clinical value to thyroid cancer patients harboring a low risk of distant metastases, while frequently identifying clinically insignificant findings. These data from a typical cohort of patients receiving standard thyroid cancer care provide insight into the routine use of SPECT-CT in such patients.

UPDATED AGE-SPECIFIC EXTERNAL DOSE AND EXPOSURE RATE COEFFICIENTS FOR 131I PATIENT RELEASE.

Updated effective dose rate and exposure rate coefficients for age-specific receptors representing members of the public were computed for external exposures from age-specific patients administered 131I to treat thyroid dysfunction for patient release evaluation. Coefficients were compared to the simplified point source method described by United States Nuclear Regulatory Commission Regulatory Guide (RG) 8.39, which does not consider age-specific parameters, morphometry or time-dependent 131I biodistribution. Monte Carlo age-specific phantom simulations were correlated with modified continuous voiding patient biokinetic models approximating age-specific dose and exposure rates as a function of time postadministration. Dose rates resulted in an overapproximation by a factor of ~3 from differentiated thyroid cancer patients (5% uptake) and by ~2 from hyperthyroid patients (80%) at 8h postadministration compared to RG8.39. This study provides a paradigm where age-specific morphometry and biokinetic integration must be jointly considered when developing patient release guidelines for 131I and future radionuclide therapies.

Prospective testing of clinical Cerenkov luminescence imaging against standard-of-care nuclear imaging for tumour location.

In oncology, the feasibility of Cerenkov luminescence imaging (CLI) has been assessed by imaging superficial lymph nodes in a few patients undergoing diagnostic 18F-FDG positron emission tomography / computed tomography (PET/CT). However, a weak luminescence signal required the removal of ambient light. Here, we report the development of a clinical CLI fiberscope with a lightproof enclosure, and the clinical testing of the setup using five different radiotracers. In an observational prospective trial (ClinicalTrials.gov identifier NCT03484884) involving 96 patients with existing or suspected tumours with nodal metastases and scheduled for routine clinical FDG-PET or 131I therapy, the level of agreement of CLI and standard-of-care imaging (PET or planar single-photon emission CT) for tumour location was ‘acceptable’ or higher (≥ 3 in the 1-to-5 Likert scale) for 90% of the patients. CLI correlated with the concentration of radioactive activity, and captured therapeutically relevant information from patients undergoing targeted radiotherapy or receiving the alpha emitter 223Ra, which cannot be feasibly imaged clinically. CLI could supplement radiological scans, especially when scanner capacity is limited.Prospective testing of a clinical fiberscope with a lightproof enclosure for Cerenkov luminescence imaging using five different radiotracers showed satisfactory agreement with standard-of-care nuclear imaging for tumour location.

Analysis of the Correlation between the Radioactive Iodine Activity and Neutrophil-to-Lymphocyte Ratio in Patients with Differentiated Thyroid Cancer.

Simple SummaryA higher tumor burden in patients with differentiated thyroid cancer undergoing radioactive iodine (131I) therapy may release into the bloodstream large amounts of 131I with a long residence time. We hypothesized that after the 131I intake, the blood concentration of 131I shows a course in several phases. To our knowledge, this research is the first of its kind. The results of the current study demonstrated a 131I blood concentration biphasic course. The time points to be considered are 46 and 69 h. 131I uptake in the residual thyroid tissue peaked after 46 h. The positive correlation between the neutrophil-to-lymphocyte ratio and administered 131I activity or the blood activity shows that the time interval between 46 and 69 h should be associated with the release of hematological inflammatory mediators, such as neutrophils and lymphocytes, to eradicate tumor cells in response to 131I therapy.Publications investigating the effect of radioactive iodine (131I) therapy on the circulating peripheral blood cells in patients with differentiated thyroid cancer (DTC) are limited to blood samples collected more than 92 h after 131I. Studies conducted on blood samples collected up to 92 h are rare due to the radioactive contamination risk. This research aimed to assess the relationship between the prescribed 131I activity, human whole blood activity, and peripheral blood cells at many time points (6, 22, 46, 69, and 92 h after 131I). The study enrolled 50 female patients with DTC who received a 131I median activity of 90.54 mCi (3.35 GBq). The neutrophil-to-lymphocyte ratio (NLR) was measured as an inflammatory marker. 131I uptake in the residual thyroid tissue peaked after 46 h. Blood activity decreased in the first 46 h and increased 69 h after the 131I intake. Blood activity was associated with the absolute lymphocyte count and the NLR at 69 h (r = −0.49 and r = 0.52, p < 0.001). Our results demonstrate that the time interval between 46 and 69 h should be associated with the release of hematological inflammatory mediators, such as neutrophils and lymphocytes, to eradicate tumor cells in response to 131I therapy.

Combination of Stimulated Thyroglobulin and Antithyroglobulin Antibody Predicts the Efficacy and Prognosis of 131I Therapy in Patients With Differentiated Thyroid Cancer Following Total Thyroidectomy: A Retrospective Study.

Background and PurposeThis study aimed to analyze the diagnostic ability of the combination of stimulated thyroglobulin (sTg) and antithyroglobulin antibody (TgAb) in predicting the efficacy and prognosis of radioactive iodine (131I) therapy (RAIT) in patients with differentiated thyroid carcinomas (DTCs) after total thyroidectomy (TT).MethodsThis retrospective study comprised 409 DTC patients who underwent 131I treatment following TT in the First Affiliated Hospital of Zhengzhou University from January 2019 to August 2020, and they were followed up to November 2021. Patients were divided into the successful ablation and the unsuccessful ablation group based on the classification of the efficacy of RAIT in the 2015 American Thyroid Association guidelines. The clinical characteristics and the efficacy of the initial RAIT were evaluated. The cutoffs of preablation sTg, sTg/thyroid-stimulating hormone (TSH) ratio, and sTg×TgAb product were calculated to predict the efficacy of RAIT. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors for unsuccessful ablation. Kaplan–Meier curves were used to estimate the prognostic value of sTg×TgAb product affecting progression-free survival (PFS).ResultsThe cohort consisted of 222 cases in the successful ablation group and 187 cases in the unsuccessful ablation group. Between the two groups, preablation sTg, sTg/TSH ratio, and sTg×TgAb product were significantly higher in the unsuccessful ablation group. The area under the curve (AUC) of the sTg×TgAb product was the highest among the above three factors. The cutoffs for the worse therapeutic effect of the initial RAIT in sTg, sTg/TSH ratio, and sTg×TgAb were >2.99 ng/ml, >0.029 mg/IU, and >34.18, respectively. STg >2.99 ng/ml and sTg×TgAb product >34.18 were independent risk factors for unsuccessful ablation. Patients with sTg×TgAb product >34.18 had shorter PFS than that of patients with sTg×TgAb product ≤34.18. In separate analyses of TgAb-negative and TgAb-positive subgroups, higher sTg×TgAb was both associated with a lower success rate of RAIT and a shorter PFS.ConclusionSTg×TgAb product predicted the efficacy and prognosis of 131I therapy for both TgAb-negative and TgAb-positive DTC patients before the initial 131I treatment following TT. Thus, it can be used as a clinical reference indicator for the surveillance of DTC patients.

Second primary malignancy risk in thyroid cancer and matched patients with and without radioiodine therapy analysis from the observational health data sciences and informatics.

Risk of second primary malignancy (SPM) after radioiodine (RAI) therapy has been continuously debated. The aim of this study is to identify the risk of SPM in thyroid cancer (TC) patients with RAI compared with TC patients without RAI from matched cohort. Retrospective propensity-matched cohorts were constructed across 4 hospitals in South Korea via the Observational Health Data Science and Informatics (OHDSI), and electrical health records were converted to data of common data model. TC patients who received RAI therapy constituted the target group, whereas TC patients without RAI therapy constituted the comparative group with 1:1 propensity score matching. Hazard ratio (HR) by Cox proportional hazard model was used to estimate the risk of SPM, and meta-analysis was performed to pool the HRs. Among a total of 24,318 patients, 5,374 patients from each group were analyzed (mean age 48.9 and 49.2, women 79.4% and 79.5% for target and comparative group, respectively). All hazard ratios of SPM in TC patients with RAI therapy were ≤ 1 based on 95% confidence interval(CI) from full or subgroup analyses according to thyroid cancer stage, time-at-risk period, SPM subtype (hematologic or non-hematologic), and initial age (< 30years or ≥ 30years). The HR within the target group was not significantly higher (< 1) in patients who received over 3.7GBq of I-131 compared with patients who received less than 3.7GBq of I-131 based on 95% CI. There was no significant difference of the SPM risk between TC patients treated with I-131 and propensity-matched TC patients without I-131 therapy.

The Value of 99mTc-MIBI SPECT/CT in the Postoperative Assessment of Patients with Differentiated Thyroid Carcinoma.

The therapeutic approaches of differentiated thyroid carcinoma (DTC) are surgery, ablation therapy with the postoperative use of radioiodine-131 (131I), and thyroid-stimulating hormone (TSH) suppression therapy. After the surgical therapy, the patient should be assessed for remnants/metastases. The purpose of this research was to investigate the role of technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) single photon emission computed tomography/computed tomography (SPECT/CT) in the postoperative management of patients with DTC. The study comprised 22 DTC patients (13 women, 9 men; mean age 46.55 ± 13.27 y) who underwent a total thyroidectomy previously. All patients were investigated for thyroid remnants/ metastases by99mTc-MIBI SPECT/CT, posttherapy 131I whole-body scan (WBS) and ultrasound (US). Serum TSH, thyroglobulin and anti-Tg antibody levels were measured. Results of imaging modalities and laboratory measurements were compared with each other. 99mTc-MIBI SPECT/CT, 131I WBS and US respectively demonstrated thyroid remnants in 15 (68.18%), 22 (100%) and 14 (63.63%) of all patients and metastatic lymph nodes in 8 (100%), 6 (75%) and 6 (75%) of the 8 patients with lymph node metastases.99mTc-MIBI SPECT/CT also demonstrated lung metastases in 2 patients (9.09% of all patients). The same result was obtained with 131I WBS. The findings of this study show that 99mTc-MIBI SPECT/CT can be effective for detecting metastases in patients with DTC who underwent surgery prior to 131I therapy.

Analysis of correlation factors influencing the outcome of initial 131I remnant ablative therapy in intermediate- to high-risk patients with papillary thyroid microcarcinoma.

To investigate the factors influencing the outcome of initial 131I remnant ablative therapy in intermediate- to high-risk patients with papillary thyroid microcarcinoma (PTMC). We divided 99 patients with PTMC who underwent total thyroidectomy into two groups according to their response to initial 131I remnant ablative therapy: excellent response (ER) and non-ER groups. Clinical and laboratory characteristics were collected and retrospectively analyzed using univariate and multivariate binary logistic regression. Receiver operator characteristic (ROC) curves and diagnostic cutoff values were analyzed to evaluate the predictive value of significant quantitative influencing factors for 131I treatment outcomes. A prognostic nomogram model based on the above independent risk factors was established. Of the 99 eligible patients who accepted the initial 131I treatment following total thyroidectomy, 76 (76.7%) were classified into the ER group and 23 (23.3%) into the non-ER group. The univariate and multivariate analyses showed that extrathyroidal extension [ETE; odds ratio (OR) = 4.769; P = 0.041], preablative thyrotropin (TSH; OR = 0.972; P = 0.017), and stimulated thyroglobulin (sTg; OR = 1.614; P = 0.040) were independent predictors for the therapeutic effect of 131I treatment. Patients with higher sTg (>1.37 ng/ml) and lower TSH (<67.97 mU/l) and ETE tended to have a poor response to initial 131I treatment. The quantification of the therapeutic effect of initial 131I therapy in patients with PTMC using our newly constructed nomogram showed that ETE, preablative sTg, and TSH were contributors to non-ER. Intermediate- to high-risk patients with PTMC after total thyroidectomy who had low pretreatment sTg and high preablative TSH levels and negative ETE were more likely to achieve satisfactory response to initial 131I remnant ablative therapy. Our prognostic nomogram is a valuable tool to enable patients and clinical professionals to be better informed about patients' therapeutic response to initial 131I remnant ablative therapy.

Adjuvant I-131 therapy for T0-3 N1b M0 differentiated thyroid cancer with many (≥ 5) positive nodes.

BackgroundIn patients with well-differentiated thyroid cancer, there is controversy about the prognostic importance of a large number of positive neck nodes and the potential value of radioiodine therapy. The purpose of this study was to evaluate this issue in the group of patients for whom it is most clinically important — those with classic histology and favorable T and M stage.Materials and methodsTwenty-five patients met the following inclusion criteria: classic histology of papillary or follicular thyroid carcinoma treated with total thyroidectomy and neck dissection followed by adjuvant I-131 treatment in our department between January 1, 2003, and December 31, 2013; adult age of > 21 years; and American Joint Committee on Cancer (AJCC ) stage (8th edition) of T0–3, N1b with ≥ 5 positive nodes, and M0.ResultsThe median positive node number was 10 (range, 5–31). The median adjuvant I-131 dose was 158 mCi (range, 150–219 mCi). The median follow-up in patients without recurrence after treatment was 7.3 years. The 10-year actuarial rates were favorable: overall survival, 100%; freedom from visible recurrence, 82%; and visible or biochemical recurrence, 72%.ConclusionRecurrence was infrequent in our study population with ≥ 5 positive nodes following moderate-dose adjuvant I-131 treatment. These results are valuable in directing initial adjuvant therapy and follow-up intensity. Our results do not inform the question of the use of postoperative thyroglobulin (Tg) level to select N1b patients for low-dose I-131 treatment.

Surgical Management of Low-/Intermediate-Risk Node Negative Thyroid Cancer: A Single-Institution Study Using Propensity Matching Analysis to Compare Thyroid Lobectomy and Total Thyroidectomy

Background: The approach for surgical treatment of patients with low-/intermediate-risk T1T2N0/Nx well-differentiated thyroid cancer (WDTC)-total thyroidectomy (TT) versus thyroid lobectomy (TL)-remains a controversial topic. Conducting a randomized controlled trial (RCT) would be the gold standard to address this issue. However, this is challenging due to excellent survival outcomes, and therefore, high number of patients and long-term follow-up would be required. As an alternative to RCT, we have used propensity score (PS) matching to determine if T1T2N0/Nx patients selected to have TL had equivalent outcomes to a similar group treated with TT. Methods: After institutional review board approval, a database of 6259 patients with WDTC treated with primary surgery at our institution between 1985 and 2016 was analyzed to identify patients with T1T2N0/Nx cancers. Of 3756 patients identified, 943 were managed by TL and 2813 by TT. To control for possible confounders and reduce potential bias, we selected age, sex, histology, 131I therapy, American Thyroid Association risk, and American Joint Committee Cancer stage as our PS matching criteria. Subsequently, 918 TL patients were successfully matched with 918 TT patients. The Pearson χ2 test or Fisher's exact test was used to compare categorical covariates, and Student's t-test was used for comparison of continuous variables between the two groups. Disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: After PS matching, there were no significant differences between TL and TT patients for OS (10-year OS: 92.2% vs. 91.3%, p = 0.9668), DSS (10-year DSS: 100% vs. 99.1%, p = 0.1967), or RFS (10-year RFS: 99.5% vs. 98.3%, p = 0.079). Conclusions: For low-/intermediate-risk patients with intrathyroidal thyroid cancer <4 cm, patients selected for TL have similar survival outcomes to a comparable group treated by TT.

Poorly differentiated thyroid carcinoma: a clinician's perspective.

Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid carcinoma originating from follicular epithelial cells. No explicit consensus can be achieved to date due to sparse clinical data, potentially compromising the outcomes of patients. In this comprehensive review from a clinician’s perspective, the epidemiology and prognosis are described, diagnosis based on manifestations, pathology, and medical imaging are discussed, and both traditional and emerging therapeutics are addressed as well. Turin consensus remains the mainstay diagnostic criteria for PDTC, and individualized assessments are decisive for treatment option. The prognosis is optimal if complete resection is performed at early stage but dismal in nearly half of patients with locally advanced and/or distant metastatic diseases, in which adjuvant therapies such as 131I therapy, external beam radiation therapy, and chemotherapy should be incorporated. Emerging therapeutics including molecular targeted therapy, differentiation therapy, and immunotherapy deserve further investigations to improve the prognosis of PDTC patients with advanced disease.

I-124 PET/CT image-based dosimetry in patients with differentiated thyroid cancer treated with I-131: correlation of patient-specific lesional dosimetry to treatment response.

The objective of this study is to evaluate the lesion absorbed dose (AD), biological effective dose (BED), and equivalent uniform dose (EUD) to clinical-response relationship in lesional dosimetry for 131I therapy. Nineteen lesions in four patients with metastatic differentiated thyroid cancer (DTC) were evaluated. The patients underwent PET/CT imaging at 2h, 24h, 48h, 72h, and 96h post administration of ~ 33-65MBq (0.89-1.76mCi) of 124I before undergoing 131I therapy. The 124I PET/CT images were used to perform dosimetry calculations for 131I therapy. Lesion dose-rate values were calculated using the time-activity data and integrated over the measured time points to obtain AD and BED. The Geant4 toolkit was used to run Monte Carlo on spheres the same size as the lesions to estimate EUD. The lesion AD, BED, and EUD values were correlated with response data (i.e. change in lesion size pre- and post-therapy): complete response (CR, i.e. disappearance of the lesion), partial response (PR, i.e. any decrease in lesion length), stable disease (SD, i.e., no change in length), and progressive disease (PD, i.e., any increase in length). The lesion responses were CR and PR (58%, 11/19 lesions), SD (21%, 4/19), and PD (21%, 4/19). For CR and PR lesions, the ADs, BEDs and EUDs were > 75Gy for 82% (9/11) and < 75Gy for 18% (2/11). The ADs and BEDs were < 75Gy for SD and PD lesions. By performing retrospective dosimetry calculations for 131I therapy based on 124I PET/CT imaging, we evaluated the correlation of three dosimetric quantities to lesional response. When lesion AD, BED, and EUD values were > 75Gy, 47% (9/19) of the lesions had a CR or PR. The AD, BED, and EUD values for SD and PD lesions were < 75Gy. The data presented herein suggest that the greater the lesion AD, BED, and/or EUD, the higher the probability of a therapeutic response to 131I therapy.

Analysis of Short-Term and Stable DNA Damage in Patients with Differentiated Thyroid Cancer Treated with 131I in Hypothyroidism or with Recombinant Human Thyroid-Stimulating Hormone for Remnant Ablation.

It is well known that ionizing radiation can induce genetic damage and that oxidative stress is a major factor inducing it. Our aim was to investigate whether thyroid remnant ablation with low activities of 131I (1,850 MBq) is associated with DNA damage by evaluating the CometAssay, micronuclei, and chromosome aberrations with multicolor fluorescent in situ hybridization. Methods: We studied 62 patients prepared with recombinant human thyroid-stimulating hormone (rhTSH) or by thyroid hormone withdrawal. In both groups, we analyzed stable and unstable genetic alterations before 131I therapy and 1 wk and 3 mo after 131I administration. We also correlated the genetic damage with several variables, including the degree of radiation-induced oxidative stress, genetic polymorphisms of enzymes involved in DNA repair, and antioxidative stress. Results: We found a comparable amount of DNA breaks evaluated by CometAssay and micronuclei testing in both groups of patients at different time points, but there was a significant increase in stable chromosome aberrations evaluated by multicolor fluorescent in situ hybridization (breaks and translocations) in patients prepared with thyroid hormone withdrawal. Overall, high chromosome damage was associated with higher retained body radioactivity and unfavorable gene polymorphism. A high level of free oxygen radicals and a low level of antioxidants were found in all patients at any time point. In particular, patients prepared with thyroid hormone withdrawal, at 3 mo, had significantly higher levels of free oxygen radicals than those prepared with rhTSH. Conclusion: An increase in stable chromosome aberrations with respect to baseline is detectable after administration of low doses of 131I in patients prepared with thyroid hormone withdrawal but not in patients prepared with rhTSH. The clinical significance of these chromosomal alterations remains to be determined.

Predictive factors for the efficacy of 131I therapy with formulated dosage calculation on Graves' disease.

To analyse predictive factors to ensure the efficacy of iodine-131 (131I) therapy on Graves' disease (GD). Graves' disease patients from three tertiary medical centers were enrolled. Serological data, thyroid mass estimation, thyroid radioactive iodine uptake, thyroid texture and thyroid murmurs (bruits) were recorded. Iodine-131 treatment was performed by applying a formulated calculation method. After one year of follow-up, GD patients with euthyroidism and hypothyroidism were classified as the cured group, and the other thyroid function status refers to the uncured group. These analyses were performed by using SPSS17.0 software. A P value of less than 0.05 was considered statistically significant. A total of 970 GD patients, of which 540 patients (55.7%) belonged to the cured group, and 430 patients (44.3%) belonged to the uncured group, participated in the current analyses. Multivariate logistic regression analysis was performed. Moreover, estimated thyroid mass, thyroid murmurs (bruits), prescribed 131I dosage, FT3 and FT4 have independent prognostic value for 131I efficacy, and their odds ratios are 1.368, 2.283, 1.326, 1.467 and 1.419, respectively. Graves' disease patients who are undergoing 131I therapy using the formulated dosage calculation could be influenced by thyroid mass, thyroid murmurs, 131I dosage and thyroid function.

Bethanechol used to prevent salivary gland dysfunction in patients submitted to radioactive iodine therapy: A double blind, placebo-controlled, randomized study

Symptoms related to salivary gland damage are one of the most frustrating complications after radioactive iodine (131I) therapy. To the best of our knowledge, this is the first study that aimed to evaluate the prophylactic effect of Bethanechol on the radioiodine content of salivary gland. Fifty patients who were referred to 131I therapy were randomized into Bethanechol and placebo groups. Patients received Bethanechol or Placebo (25 mg, 2 times daily), starting 2 h after 131I therapy to 1-month. Both groups were compared at baseline, 10, 30 and 90 days after 131I therapy based on the following: symptoms related to salivary gland damage; unstimulated whole saliva (UWS) and quality of life using University of Washington Quality of Life 4 questionnaire. Bethanechol group presented significantly lower complaints of dry mouth on 10 (p = 0.047) and 30 (p = 0.003) days compared with placebo. Salivary gland pain and swelling were more frequent among placebo patients at 10 days (p = 0.047). Comparison of the two groups by UWS, no statistical difference was found. Placebo group presented worse score related to activity (p = 0.034), saliva (p = 0.05) and humor (p = 0.05) at 10 days; palate (p = 0.05) and saliva (p = 0.05) at 1 month. Interestingly, Bethanechol patients who received 131I dose > 125mCi, showed better xerostomia indices when compared to the Placebo with same dose. Bethanechol during 131I therapy was found to be effective in decreasing the acute salivary gland damage with impact on patients' quality of life.