131I Induced In Vivo Proteolysis by Photoswitchable azoPROTAC Reinforces Internal Radiotherapy.

Photopharmacology, incorporating photoswitches such as azobenezes into drugs, is an emerging therapeutic method to realize spatiotemporal control of pharmacological activity by light. However, most photoswitchable molecules are triggered by UV light with limited tissue penetration, which greatly restricts the in vivo application. Here, this study proves that 131I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). With the presence of 50 µCi mL-1 131I, the azoPROTAC can effectively down-regulate BRD4 and c-Myc levels in 4T1 cells at a similar level as it does under light irradiation (405 nm, 60 mW cm-2). What's more, the degradation of BRD4 can further benefit the 131I-based radiotherapy. The in vivo experiment proves that intratumoral co-adminstration of 131I (300 µCi) and azoPROTC (25 mg kg-1) via hydrogel not only successfully induce protein degradation in 4T1 tumor bearing-mice but also efficiently inhibit tumor growth with enhanced radiotherapeutic effect and anti-tumor immunological effect. This is the first time that a radioisotope is successfully used as a trigger in photopharmacology in a mouse model. It believes that this study will benefit photopharmacology in deep tissue.

Enhanced antitumor immune responses via a new agent [131I]-labeled dual-target immunosuppressant.

Radionuclides theranostic are ideal "partners" for bispecific antibodies to explore the immune response of patients and synergistic treatment. A bispecific single-domain antibody-Fc fusion protein, KN046, exhibits a good treatment effect by binding to programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). An ionizing-radiation stimulus mediated by a low-dose of [131I] may be used for immunopotentiation. In this study, we established [131I]-labeled KN046 as a novel radioimmunotherapy agent to treat malignant melanoma and explored the mechanism. METHODS: After intravenous injection of [131I]-KN046, SPECT/CT imaging was applied to identify candidate targets for KN046 immunotherapy. [18F]-FDG and [68 Ga]-NOTA-GZP (granzyme B-specific PET imaging agent) micro-PET/CT imaging was used to assess the immune response in vivo after [131I]-KN046 treatment. The synergistic treatment effect of [131I]-KN046 was evaluated by exploring the [131I]-based radionuclide-induced release of tumor immunogenicity-related antigens as well as the histology and survival of tumor-bearing mice after treatment. RESULTS: The constructed [131I]-KN046 exhibited high affinity and specificity for PD-L1/CTLA-4 immune targets and had excellent in vivo intratumoral retention capability so as to achieve good antitumor efficacy. More importantly, the combination of low-dose [131I] and KN046-enhanced immunosensitivity increased the immunotherapy response rates significantly. Exposure of tumor cells to [131I]-KN046 led to upregulated expression of MHC-I and Fas surface molecules and significant increases in the degree of T-cell activation and counts of tumor-infiltrating immunocytes. CONCLUSION: Use of low-dose [131I] combined with a dual-target immunosuppressant could be exploited to identify the subset of treatment responders but also exhibited great potential for enhancing antitumor immune responses.

Safety, Biodistribution, and Dosimetry Study of Meplazumab, a Potential COVID-19 Therapeutic Drug, with 131I-Labeling and SPECT Imaging.

Coronavirus disease 2019 (COVID-19) is a serious threat to public health and is in urgent need of specific drugs. Meplazumab, a humanized monoclonal antibody targeting CD147, was confirmed to competitively block the binding between the spike of syndrome coronavirus 2 (SARS-CoV-2) and CD147, making meplazumab a promising candidate drug for COVID-19. In this study, biodistribution and dosimetry of 131I-labeled meplazumab were performed to further evaluate its potential as a therapeutic drug for COVID-19. 131I-meplazumab was both safe and tolerant in mice and healthy volunteers. A biodistribution study was performed in normal mice, and blood samples were used for pharmacokinetic analysis. Three healthy volunteers were included and subjected to single-photon-emission computed tomography (SPECT) imaging of 131I-meplazumab within 2 weeks. The distribution in mice and humans was consistent with the in vivo distribution of CD147. Biodistribution and SPECT imaging results exhibited that the liver was the organ with the highest uptake for both mice and humans. Deiodination of 131I-meplazumab can be observed in vivo, and taking Lugol's solution can protect the thyroid gland effectively. The pharmacokinetic characteristics of 131I-meplazumab in mice and humans best fit the two-compartment model. The clearance half-life (T1/2ß) in mice and humans was 117.4 and 223.5 h, respectively. The results indicated that its pharmacokinetic properties in vivo were ideal. The effective dose calculated from healthy volunteers was 0.811 ± 0.260 mSv·MBq-1, which was twice the value calculated from mice. It was safe and feasible to perform human clinical imaging experiments using a diagnostic dose of 131I-meplazumab after thyroid closure by Lugol's solution. This study will provide more experimental basis for advancing the clinical translation of meplazumab and will be valuable in evaluating therapeutic interventions for patients with COVID-19, as well as providing a reference for clinical translation studies of other antibody drugs.

Radioiodine treatment of pediatric Graves disease: a multicenter review.

BACKGROUND: There is no standardized approach to iodine-131 (I-131) therapy of hyperthyroidism in pediatric Graves disease. This prevents systematic study of outcomes. OBJECTIVE: To characterize current radioiodine dosing and define therapeutic outcomes at multiple institutions that use ultrasound to measure thyroid size to guide I-131 ablation of Graves disease. MATERIALS AND METHODS: This was a retrospective cohort study conducted at three institutions. The three sites collected demographic data, thyroid volume measured by ultrasound (mL), pre-ablation radioiodine uptake, I-131 activity administered, and outcomes at 6 and 12 months for children younger than 18 years of age treated with I-131 between November 2004 and October 2019. Comparisons of continuous variables were performed using the Mann-Whitney U test. RESULTS: Sixty-nine patients (mean age: 14.5±2.5 years) were included, 59 (85.5%) of whom were female. The mean administered I-131 radioiodine activity was 12.5 mCi (463 MBq) (range: 3.8-29.9 mCi [141-1,106 MBq]). At 6 months post-ablation, 54 (80.5% of 67) patients were hypothyroid, 8 (11.9% of 67) were euthyroid and 5 were hyperthyroid. Two of the five hyperthyroid patients had become euthyroid at 12 months. At 12 months, 1 previously euthyroid patient was hyperthyroid. Administered activity per mL of thyroid tissue adjusted for 24-h uptake was lower (0.18 mCi [6.7 MBq] x %/mL vs. 0.31 mCi [11.5 MBq] x %/mL, P=0.0054) for patients who remained hyperthyroid at 6 months. CONCLUSION: There is substantial variability in administered activity for radioiodine ablation of Graves disease in children. Efforts to standardize practice should start by standardizing administered activity guided by measurement of thyroid size by ultrasound. Our results and those of previous studies suggest the need for administered activities ≥0.25 mCi [9.3 MBq] x %/mL of thyroid tissue.

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine.

Fibroblast activation proteins (FAP) are overexpressed in the tumor stroma and have received attention as target molecules for radionuclide therapy. The FAP inhibitor (FAPI) is used as a probe to deliver nuclides to cancer tissues. In this study, we designed and synthesized four novel 211At-FAPI(s) possessing polyethylene glycol (PEG) linkers between the FAP-targeting and 211At-attaching moieties. 211At-FAPI(s) and piperazine (PIP) linker FAPI exhibited distinct FAP selectivity and uptake in FAPII-overexpressing HEK293 cells and the lung cancer cell line A549. The complexity of the PEG linker did not significantly affect selectivity. The efficiencies of both linkers were almost the same. Comparing the two nuclides, 211At was superior to 131I in tumor accumulation. In the mouse model, the antitumor effects of the PEG and PIP linkers were almost the same. Most of the currently synthesized FAPI(s) contain PIP linkers; however, in our study, we found that PEG linkers exhibit equivalent performance. If the PIP linker is inconvenient, a PEG linker is expected to be an alternative.

Overexpression of Both Human Sodium Iodide Symporter (NIS) and BRG1-Bromodomain Synergistically Enhances Radioiodine Sensitivity by Stabilizing p53 through NPM1 Expression.

Improved therapeutic strategies are required to minimize side effects associated with radioiodine gene therapy to avoid unnecessary damage to normal cells and radiation-induced secondary malignancies. We previously reported that codon-optimized sodium iodide symporter (oNIS) enhances absorption of I-131 and that the brahma-associated gene 1 bromodomain (BRG1-BRD) causes inefficient DNA damage repair after high-energy X-ray therapy. To increase the therapeutic effect without applying excessive radiation, we considered the combination of oNIS and BRG1-BRD as gene therapy for the most effective radioiodine treatment. The antitumor effect of I-131 with oNIS or oNIS+BRD expression was examined by tumor xenograft models along with functional assays at the cellular level. The synergistic effect of both BRG1-BRD and oNIS gene overexpression resulted in more DNA double-strand breaks and led to reduced cell proliferation/survival rates after I-131 treatment, which was mediated by the p53/p21 pathway. We found increased p53, p21, and nucleophosmin 1 (NPM1) in oNIS- and BRD-expressing cells following I-131 treatment, even though the remaining levels of citrulline and protein arginine deiminase 4 (PAD4) were unchanged at the protein level.

Close contact restriction periods for patients who have received iodine-131 therapy for differentiated thyroid cancer.

Patients treated with radionuclide therapy usually require restrictions on certain activities for a period of time following treatment to optimise protection of the public and ensure the legal dose limit is not exceeded. Software may be used to calculate necessary restriction periods for an individual based on longitudinal dose rate measurements from the time of radiopharmaceutical administration. A spreadsheet program has been used for this purpose in Australian hospitals for the last two decades. However, this spreadsheet has a limitation in that it uses an approximation in the calculation of dose from a contact pattern, which affects the calculated restriction period. A computer program called Dorn was developed that provides the same functionality as the spreadsheet but without this approximation. Proffered radiation safety advice from Dorn and the spreadsheet were compared. Advice from the spreadsheet and Dorn were compared for 55 patients who underwent iodine-131 therapy for differentiated thyroid cancer. The restriction periods for caring for infants, close contact with children and sleeping with a partner were typically about 13 h longer in Dorn than in the spreadsheet, but in some cases were over a week shorter or a month longer. If the Dorn program is used clinically in place of the spreadsheet, some patients will enjoy shorter restriction periods and the therapy provider can be more confident in their compliance with regulatory requirements and best practice. Dorn is freely available fromhttps://doi.org/jg5f.

Radiological study of a wastewater treatment plant associated with radioiodine therapy at a hospital in West Java, Indonesia.

Nuclear medicine (NM) services in Indonesia have rapidly developed due to the increasing number of patients, and this growth has been supported by standardized regulations in the field, including the management of solid waste generated. However, multiple reports indicate that licensing control does not regulate liquid waste disposal from patient excretions to protect personnel and the community from radiopharmaceutical exposure. One of the radiopharmaceuticals commonly used in NM and having the longest half-life among the radiopharmaceuticals used in NM is iodine 131(I-131). Thus, this study used a high-purity germanium detector to measure iodine-131 (I-131) activity in liquid waste from decay tanks, temporary collection channels, the hospital's wastewater treatment plant (WWTP) outlet, and six points around the NM service and liquid waste treatment unit. Concentration measurements in three decay tanks were carried out sequentially every 12 h for 3 d, corresponding to the therapy period. The results showed that the I-131 activity levels in the decay tanks and temporary collection channels, before being mixed with liquid waste from other units, were 95.9 × 106± 4.4 × 106Bq m-3.At the point where the liquid waste from other units was mixed, the activity level decreased significantly to 472 680 ± 22 160 Bq m-3, which was below the clearance level of 107Bq m-3. However, the recorded concentration exceeded the standard for environmental radioactivity at the hospital's WWTP outlet, namely 37 670 ± 2040 Bq m-3. The measurement results for I-131 in the air in the open space for two nuclear buildings was above the standard at 1.3 ± 0.27 Bq m-3. According to the RESRAD simulation, based on the initial dose taken from the liquid waste treatment outlet point, the accumulation of doses and the risk of cancer among workers and the community decreased within 3 months after the maximum exposure.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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 (< 30 years or ≥ 30 years). The HR within the target group was not significantly higher (< 1) in patients who received over 3.7 GBq of I-131 compared with patients who received less than 3.7 GBq of I-131 based on 95% CI. CONCLUSION: 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.

New Directions in Treatment of Metastatic or Advanced Pheochromocytomas and Sympathetic Paragangliomas: an American, Contemporary, Pragmatic Approach.

PURPOSE OF REVIEW: Multiple therapies with novel mechanisms have been explored in clinical trials for the treatment of metastatic pheochromocytomas and paragangliomas. We review current and future therapies for this disease and provide guidance on how and when to prescribe them based on tumor progression, clinical manifestations, molecular features, and social factors. RECENT FINDINGS: Approximately 60-70% of metastatic pheochromocytomas and paragangliomas express the noradrenaline transporter in their cell membranes. High specific activity iodine-131 metaiodobenzylguanidine has been recently approved by the US Food and Drug Administration for the treatment of metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter, in patients aged ≥ 12 years. More than 90% of patients treated with this medication exhibit clinical benefits. However, other therapies with novel mechanisms of action are needed to help all patients with this disease. Treatment of metastatic pheochromocytomas and paragangliomas is recommended based on the severity of symptoms, the progression of the disease, and the patient's performance status. Currently available therapies include surgery; systemic chemotherapy with cyclophosphamide, vincristine, and dacarbazine, or with temozolomide; high specific activity iodine-131 metaiodobenzylguanidine; peptide receptor radionuclide therapy; immunotherapy; tyrosine kinase inhibitors; and hypoxia-inducible factor 2 alpha inhibitors. Financial and social factors such as health insurance coverage and disparities also impact current clinical practice in the USA.

Predictors of Hypothyroidism Following Empirical Dose Radioiodine in Toxic Thyroid Nodules: Real-Life Experience.

OBJECTIVE: We aimed to determine the factors predicting hypothyroidism after radioactive iodine (RAI) treatment in patients with toxic adenoma and toxic multinodular goiter. METHODS: We retrospectively collected the data of 237 patients with toxic multinodular goiter or toxic adenoma who had consecutively received RAI treatment between 2014 and 2020 at 2 medical centers. Patients who received the second RAI treatment and whose medical records could not be accessed were excluded from the study. Finally, 133 patients were included in the study. RAI was administered at an empirical dose of 15 or 20 mCi. RESULTS: The median age of the 133 participants was 69 years (interquartile range, 62-75 years), and 64.7% of the participants were women. A total of 42.1% of the patients had toxic adenoma, whereas 57.9% of patients had toxic multinodular goiter. The median follow-up was 24 months (interquartile range, 11-38 months). During the follow-up, 61.7% of patients became euthyroid, 30.8% developed hypothyroidism, and 7.5% remained hyperthyroid. The median month of hypothyroidism onset was 4 months (interquartile range, 2-9 months). Regression analysis revealed 2 factors that could predict hypothyroidism: thyroid-stimulating hormone (odds ratio, 2.548; 95% CI, 1.042-6.231; P = .04) and thyroid volume (odds ratio, 0.930; 95% CI, 0.885-0.978; P = .005). CONCLUSION: Overall, 30.8% of the cases developed hypothyroidism after the RAI treatment. Approximately 78% of hypothyroidism developed within the first 10 months. The risk of hypothyroidism was higher in patients with higher thyroid-stimulating hormone and smaller thyroid volume.

THE OCCURRENCE OF ACUTE PANCREATITIS AFTER IODINE 131 TREATMENT OF HYPERTHYROIDISM.

Acute pancreatitis is a common and potentially fatal gastrointestinal disease. We report a case of acute pancreatitis induced by iodine-131 therapy for hyperthyroidism. Iodine 131 is distributed through the blood, so it can accumulate and damage normal tissues in other parts of the body that are involved in thyroid hormone metabolis.

The clinical significance of remnant thyroid tissue in thyroidectomized differentiated thyroid cancer patients on 131I-SPECT/CT.

BACKGROUND: To explore the 131I-SPECT/CT characteristics of remnant thyroid tissue (RTT) in differentiated thyroid cancer (DTC), further assess the risk factors and clinical significance. METHODS: 52 DTC patients after total thyroidectomy had undergone neck 131I-SPECT/CT before 131I ablation. The diagnosis of RTT was based on SPECT/CT and follow-up at least 3 months. The anatomic locations and features of SPECT/CT of RTT were assessed by reviewers. The risk factors of RTT with CT positive were analyzed by the chi-square test. RESULTS: A total of 80 lesions of RTT were diagnosed in this study, most of them were mainly located in the regions adjacent to trachea cartilage (37/80) or lamina of thyroid cartilage (17/80). On SPECT/CT of RTT, low, moderate and high uptake were respectively noted in 10, 24 and 46 lesions, definite positive, suspected positive and negative CT findings were respectively noted in 10, 21 and 49. The RTT lesions with definite positive CT findings were mainly located adjacent to lamina of thyroid cartilage (5/10). Primary thyroid tumor (P = 0.029) and T stage (P = 0.000) were the effective risk factors of CT positive RTT. CONCLUSIONS: RTT has certain characteristic distribution and appearances on SPECT/CT. Most of RTT with definite CT abnormalities located adjacent to lamina of thyroid cartilage, which suggest surgeons should strengthen the careful removal in this region, especially primary thyroid tumor involving bilateral and T4 stage. This study can provide a certain value for the improvement of thyroidectomy quality in DTC patients.

Thyroid doses in Ukraine due to 131I intake after the Chornobyl accident. Report I: revision of direct thyroid measurements.

The increased risk of thyroid cancer among individuals exposed during childhood and adolescence to Iodine-131 (131I) is the main statistically significant long-term effect of the Chornobyl accident. Several radiation epidemiological studies have been carried out or are currently in progress in Ukraine, to assess the risk of radiation-related health effects in exposed populations. About 150,000 measurements of 131I thyroid activity, so-called 'direct thyroid measurements', performed in May-June 1986 in the Ukrainian population served as the main sources of data used to estimate thyroid doses to the individuals of these studies. However, limitations in the direct thyroid measurements have been recently recognized including improper measurement geometry and unknown true values of calibration coefficients for unchecked thyroid detectors. In the present study, a comparative analysis of 131I thyroid activity measured by calibrated and unchecked devices in residents of the same neighboring settlements was conducted to evaluate the correct measurement geometry and calibration coefficients for measuring devices. As a result, revised values of 131I thyroid activity were obtained. On average, in Vinnytsia, Kyiv, Lviv and Chernihiv Oblasts and in the city of Kyiv, the revised values of the 131I thyroid activities were found to be 10-25% higher than previously reported, while in Zhytomyr Oblast, the values of the revised activities were found to be lower by about 50%. New sources of shared and unshared errors associated with estimates of 131I thyroid activity were identified. The revised estimates of thyroid activity are recommended to be used to develop an updated Thyroid Dosimetry system (TD20) for the entire population of Ukraine as well as to revise the thyroid doses for the individuals included in post-Chornobyl radiation epidemiological studies: the Ukrainian-American cohort of individuals exposed during childhood and adolescence, the Ukrainian in utero cohort and the Chornobyl Tissue Bank.

Clinical applications of single-photon emission computed tomography/computed tomography in post-ablation 131iodine scintigraphy in children and young adults with differentiated thyroid carcinoma.

BACKGROUND: The utility of integrated single-photon emission computed tomography/computed tomography (SPECT/CT) in children and young adults with differentiated thyroid carcinoma is incompletely studied. OBJECTIVE: To determine the value of adding SPECT/CT to conventional whole-body scintigraphy in post-ablation iodine-131 (131I) scintigraphy for children and young adults with differentiated thyroid carcinoma. MATERIALS AND METHODS: Planar scintigraphy and SPECT/CT were performed on 42 post-surgical children and young adults (32 female, 10 male; mean age 14.3±4.9 years, range 7-20 years) with differentiated thyroid carcinoma (39 papillary, 2 follicular, 1 mixed) 5 days after the therapeutic administration of 1.9-7.4 GBq of 131I. Planar and SPECT/CT images were interpreted independently, and sites of uptake were categorized as positive or equivocal with respect to thyroid bed, lymph node and distant metastasis uptake. An experienced thyroid endocrinologist used a combination of surgical histopathology and scintigraphic findings to determine whether the addition of SPECT/CT would change patient management. RESULTS: Planar scintigraphy evidenced 88 radioiodine-avid foci and SPECT/CT confirmed all foci. No additional foci were disclosed by SPECT/CT. SPECT/CT correctly classified 16/88 (18%) foci that were unclear or wrongly classified at planar scintigraphy. Globally, SPECT/CT showed an incremental value over planar scintigraphy in 9 (21.4%) patients and changed therapeutic management in 3 (7.1%; 95% confidence interval, 2-20%) patients. CONCLUSION: SPECT/CT improved localization and characterization of focal 131I uptake on post-ablation whole-body scintigraphy in children and young adults with differentiated thyroid carcinoma. Further prospective evaluation in a larger series is justified to prove the effect of post-ablation SPECT/CT-based management decisions.

Use of radioiodine in nuclear medicine-A brief overview.

Radioiodines have a long history in nuclear medicine. Herein, we discuss the production, properties and applications of these versatile iodine-based imaging and theragnostic agents. There are 38 isotopes of iodine (I) including one stable form (127 I). The most common radionuclides used in medical imaging and treatment, including Iodine-123 (123 I), Iodine-124 (124 I), Iodine-125 (125 I) and Iodine-131 (131 I), are discussed in this review.

Radiation exposure to allied health personnel handling blood specimens from patients receiving radioactive iodine-131 and recombinant human TSH (thyrogen®) stimulation.

With increasing use of recombinant human TSH (rhTSH) stimulation protocol in radioactive iodine-131 treatment of thyroidectomised differentiated thyroid carcinoma (DTC), there is increasing concern regarding radiation safety during collection and processing of radioactive blood samples. Our study aims to quantify this radiation exposure in the context of current radiation guidelines to provide a practical safety framework. We analysed 45 patients prospectively referred to a tertiary centre in Singapore, who had histologically proven DTC, and who were thyroidectomised and planned for I-131 with rhTSH stimulation. Each patient received rhTSH for two consecutive days, with I-131 administered 24 h after, and a stimulated Thyroglobulin blood sample collected and processed 72 h after the last rhTSH dose. We measured radiation exposures with dosimeters. Based on the average and maximum exposure rates calculated, we extrapolated and derived the number of radioactive blood samples that could be safely collected and processed. Mean hand and body radiation exposures during venepuncture and blood processing were generally significantly higher than background radiation. Based on average exposure rates, the permissible number of blood samples that can be collected and processed is 9.09 × 103per year (24 per day) and 8.70 × 104per year (238 per day), respectively. This is the first study to date to extrapolate permissible thresholds that can serve as a practical guideline to the number of radioactive blood samples which can be safely collected and processed, following radioactive iodine therapy, within the limits of current radiation guidelines. Once validated, generalisations to other radioactive therapies may be considered.

Smart 131 I-Labeled Self-Illuminating Photosensitizers for Deep Tumor Therapy.

Stimulating photosensitizers (PS) by Cerenkov radiation (CR) can overcome the light penetration limitation in traditional photodynamic therapy. However, separate injection of radiopharmaceuticals and PS cannot guarantee their efficient interaction in tumor areas, while co-delivery of radionuclides and PS face the problem of nonnegligible phototoxicity in normal tissues. Here, we describe a 131 I-labeled smart photosensitizer, composed of pyropheophorbide-a (photosensitizer), a diisopropylamino group (pH-sensitive group), an 131 I-labeled tyrosine group (CR donor), and polyethylene glycol, which can self-assemble into nanoparticles (131 I-sPS NPs). The 131 I-sPS NPs showed low phototoxicity in normal tissues due to aggregation-caused quenching effect, but could self-produce reactive oxygen species in tumor sites upon disassembly. Upon intravenous injection, 131 I-sPS NPs showed great tumor inhibition capability in subcutaneous 4T1-tumor-bearing Balb/c mice and orthotopic VX2 liver tumor bearing rabbits. We believed 131 I-sPS NPs could expand the application of CR and provide an effective strategy for deep tumor theranostics.

Contemporary considerations in adjuvant radioiodine treatment of adults with differentiated thyroid cancer.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy with a growing incidence worldwide. The initial conventional management is surgery, followed by consideration of 131 I treatment that includes three options. These are termed remnant ablation (targeting benign thyroid remnant), adjuvant (targeting presumed microscopic DTC) and known disease (targeting macroscopic DTC) treatments. Some experts mostly rely on clinicopathologic assessment for recurrence risk to select patients for the 131 I treatment. Others, in addition, apply radioiodine imaging to guide their treatment planning, termed theranostics (aka theragnostics or radiotheragnostics). In patients with low-risk DTC, remnant ablation rather than adjuvant treatment is generally recommended and, in this setting, the ATA recommends a low 131 I activity. 131 I adjuvant treatment is universally recommended in patients with high-risk DTC (a primary tumor of any size with gross extrathyroidal extension) and is generally recommended in intermediate-risk DTC (primary tumor >4 cm in diameter, locoregional metastases, microscopic extrathyroidal extension, aggressive histology or vascular invasion). The optimal amount of 131 I activity for adjuvant treatment is controversial, but experts reached a consensus that the 131 I activity should be greater than that for remnant ablation. The main obstacles to establishing timely evidence through randomized clinical trials for 131 I therapy include years-to-decades delay in recurrence and low disease-specific mortality. This mini-review is intended to update oncologists on the most recent clinical, pathologic, laboratory and imaging variables, as well as on the current 131 I therapy-related definitions and management paradigms, which should optimally equip them for individualized patient guidance and treatment.

Health-related quality of life of thyroid cancer patients undergoing radioiodine therapy: a cohort real-world study in a reference public cancer hospital in Brazil.

PURPOSE: The purpose of this study was to access changes in health-related quality of life (HRQoL) caused by radioiodine therapy (RAI) in thyroid cancer patients. METHODS: Prospective cohort study at Brazilian National Cancer Institute with patients enrolled between March 2015 and June 2017. RAI was performed by administration of 1.11 to 9.25 GBq of Na131I. EORTC QLQ-C30 v3 and EORTC QLQ-H&N35 questionnaires were applied to determine HRQoL at baseline, 1 week and 3 months after RAI. HRQoL during follow-up was evaluated by calculation of score absolute changes in each domain. Descriptive analysis was performed by measures of central tendency and dispersion. Changes in HRQoL were evaluated by paired t-test. The association between social demographic and clinical data and HRQoL was assessed by univariate linear regression for significantly changed domains, and p < 0.05 was considered significant. RESULTS: An improvement on global HRQoL and social Function post-therapy (p = 0.002 and p < 0.001) and on role (p = 0.038), emotional (p < 0.001), and cognitive function (p = 0.016) during RAI were observed. Nausea and vomiting (p < 0,001), pain (p < 0.001), sensitivity problems (p < 0.001), problems with social contact (p < 0.001), dry mouth (p = 0.007), and sticky saliva (p = 0.001) increased during RAI. Females were more sensible to changes in nausea and vomiting, and patients < 55 years experienced higher changes in sense during RAI. CONCLUSIONS: Although RAI might affect HRQoL negatively, patients experienced an improvement on global HRQoL and symptoms reduction post-therapy.