Clinicopathological features affecting the efficacy in 131I ablation therapy of papillary thyroid carcinoma with lymph node metastasis.

Background: Lymph node metastasis is the major cause of increased recurrence and death in patients with papillary thyroid carcinoma (PTC). We evaluate the clinicopathologic factors affecting excellent response (ER) in patients with PTC with lymph node metastasis following operation and 131I ablation therapy. Methods: A total of 423 patients with PTC with lymph node metastasis who underwent thyroidectomy and postoperative 131I ablation therapy were enrolled. The relationship between clinicopathological factors affecting ER achievement was analyzed. Results: Multivariate analysis showed that the foci diameter (≤1 cm), unifocal, combination with Hashimoto's thyroiditis (HT), lymph node metastases rate (LR) (≤40%), no postoperative lymph node metastasis, low preablative stimulated thyroglobulin (ps-Tg) level (≤3.87 ng/mL), and the time of 131I ablation therapy (one time) were positively correlated with the ER achievement [odds ratio (OR): 1.744, 3.114, 3.920, 4.018, 2.074, 9.767, and 49.491, respectively; all p < 0.05]. The receiver operating characteristic (ROC) curves showed that the cutoff values of ps-Tg and LR were 4.625 ng/mL and 50.50%, respectively. The AUC of ROC of ps-Tg and LR for predicting ER achievement was 0.821 and 0.746, respectively. The Tg and the cumulative risk of non-ER elevated with the increase of LR, especially for the high-level ps-Tg (>4.625 ng/mL) group. Conclusion: The foci diameter and number, combination with HT, LR, and ps-Tg level are independent factors for ER. Ps-Tg level and LR are valid predictive factors for the efficacy of 131I therapy in patients with PTC. The predictive value of the cumulative risk of non-ER can be improved by the combination of ps-Tg and LR.

Thyroid cancer incidence in cohorts exposed in childhood to 131I released during the Windscale nuclear reactor accident at Sellafield, England, in 1957.

A fire in one of the Windscale nuclear reactors at Sellafield (Cumbria, England) in October 1957 released 1,800 TBq of 131I (half-life, 8 days) to atmosphere. Measurements of 131I activity in thyroids of exposed children showed typical thyroid doses of tens of milligray, but with some exceeding 100 mGy. Radiation exposure in childhood is known to increase the risk of thyroid cancer. Consequently, an investigation was conducted into whether raised numbers of thyroid cancer cases occurred in those exposed to 131I as young children in Cumbria. A database of Cumbrian births from 1950 onwards allowed cohorts of 56,086 births during 1950-1958 and 137,444 births during 1959-1980 to be constructed, periods including children potentially exposed and unexposed, respectively, to 131I. Three areas of Cumbria with different 131I contamination levels were identified from monitoring data, and births assigned to these three areas for the two periods of birth. Members of these six sub-cohorts were linked to incident thyroid cancer cases in Great Britain during 1981-2020 using national cancer registration databases, providing thyroid cancer incidence rates. Incidence rate ratios (IRRs), with the lowest contamination area as a reference, were computed. No IRR differed discernibly from unity. For births during 1950-1958, the IRR for the combined highest and intermediate 131I contamination areas was 0.68 (95% confidence interval: 0.24, 1.56), and no case of thyroid cancer was found in the small cohort born in the highest contamination area. In conclusion, no increased risk of thyroid cancer in those exposed to 131I as young children in Cumbria in 1957 was detected. This study adds to the evidence on the long-term risk of thyroid cancer following childhood exposure to low and moderate levels of 131I, such as occurred following the Fukushima nuclear accident in 2011.

Life-threatening amiodarone-induced thyrotoxicosis - Personalized approach to radical treatment.

Objective: Amiodarone is an iodine-rich molecule and an effective antiarrhythmic drug. It is a first-line treatment for patients with life-threatening ventricular arrhythmias and for prevention in patients at high risk. The use of amiodarone may cause serious adverse effects such as pharmacotherapy-resistant, life-threatening amiodarone-induced thyrotoxicosis (AIT)leading to rapid deterioration of the patient's condition.According to the European Thyroid Association (ETA) guidelines, emergency thyroidectomy is the first-line treatment option in these cases. ; however, is not always feasible in the clinical setting due to the high anesthetic risk.We aimed to assess the clinical course and results of urgent thyroidectomy and 131-I therapy in patients with severe AIT with worsening of cardiac status. Methods: Retrospective analysis of the clinical course and outcomes of life-threatening AIT refractory to pharmacotherapy in patients hospitalized at a tertiary endocrinology center between 2014 and 2022. Results: An electronic database search identified 75 patients hospitalized for severe AIT. At the time of AIT diagnosis, median Thyroid-stimulating hormone (TSH) concentration was 0.001 mIU/L (range 0.001-0.35), fT4 63.2 pmol/L (range 9.0 - >100), and fT3 10.2 pmol/L (range 3.8-49.3). All patients received optimal conservative treatment. Among them, 20 required urgent radical therapy due to worsening arrhythmias and/or AIT-related heart failure. In this group, 6 patients died before any radical treatment was applied, 6 underwent total thyroidectomy, while 8 patients were successfully treated with 131-I (in 6 cases after rhTSH stimulation). The median dose of 131-I used for the therapy was 784MBq (range 627-860). The decision to treat with 131-I despite low but detectable 131-I uptake (median value 6 %) was made in cases of significant contraindications to anesthesia due to refractory ventricular arrhythmias, exacerbation of severe heart failure unresponsive to cardiac treatment, myocardial infarction during AIT course, massive pulmonary embolism. Conclusion: The decision regarding the optimal time and type of radical treatment of AIT refractory to pharmacotherapy is critical for patients management and should not be delayed. Urgent therapy with 131-I may be an effective therapeutic option in patients who are unsuitable for thyroidectomy due to the high risk of anesthesia.

Effect of drying temperature on the quantitative analysis of 131I in algal samples by γ-spectrometry.

131I has been extensively utilized in nuclear medicine, resulting in its widespread detection in coastal algal samples due to its discharge. Therefore, it is essential to monitor 131I in the coastal algal samples. γ-spectrometry is an expeditious method for measuring 131I, but this method requires the pretreatment of the algal sample. The effect on 131I in the algal sample during the oven-drying treatment is unclear. In this study, the Laminaria japonica Areschoug and Sargassum vachellianum Greville were collected at two locations and analyzed for 131I using γ-spectrometry. Additionally, the content of iodine was measured using an Inductively Coupled Plasma-Mass Spectrometer (ICP-MS) to clarify the effect of 131I loss during drying treatment at different temperatures. The results demonstrated that the dried Laminaria and Sargassum samples had calculated 131I activity concentration relative standard deviations (RSDs) of 6.34 % and 16.31 %, respectively, while the fresh samples exhibited RSDs of 11.70 % and 15.57 %. Additionally, the iodine content RSDs in the dried samples were 9.19 % for Laminaria and 10.34 % for Sargassum. Significantly, discrepancies in 131I activity concentration between the fresh and dried Laminaria and Sargassum were 5.4 % and 10.3 %. These findings indicate that the temperature factor in drying has no effect on 131I loss in Laminaria and Sargassum in the range of 70 °C-110 °C.

Early and long-term responses of intestinal microbiota and metabolites to 131I treatment in differentiated thyroid cancer patients.

BACKGROUND: Multiple high doses of 131I therapy in patients with differentiated thyroid cancer (DTC) might disrupt the balance of gut microbiota and metabolites. This study aimed to investigate the alterations of intestinal bacteria and metabolism over two courses of 131I therapy, explore the interactions, and construct diagnostic models reflecting enteric microecology based on 131I therapy. METHODS: A total of 81 patients were recruited for the first 131I therapy (131I-1st), among whom 16 received a second course (131I-2nd) after half a year. Fecal samples were collected 1 day before (Pre-131I-1st/2nd) and 3 days after (Post-131I-1st/2nd) 131I therapy for microbiome (16S rRNA gene sequencing) and metabolomic (LC-MS/MS) analyses. RESULTS: A total of six microbial genera and 11 fecal metabolites enriched in three pathways were identified to show significant differences between Pre-131I-1st and other groups throughout the two courses of 131I treatment. In the Post-131I-1st group, the beneficial bacteria Bifidobacterium, Lachnoclostridium, uncultured_bacterium_f_Lachnospiraceae, and Lachnospiraceae_UCG004 were abundant and the radiation-sensitive pathways of linoleic acid (LA), arachidonic acid, and tryptophan metabolism were inhibited compared with the Pre-131I-1st group. Compared with the Pre-131I-1st group, the Pre-131I-2nd group exhibited a reduced diversity of flora and differentially expressed metabolites, with a low abundance of beneficial bacteria and dysregulated radiation-sensitive pathways. However, less significant differences in microbiota and metabolites were found between the Pre/Post-131I-2nd groups compared with those between the Pre/Post-131I-1st groups. A complex co-occurrence was observed between 6 genera and 11 metabolites, with Lachnoclostridium, Lachnospiraceae_UCG004, Escherichia-Shigella, and LA-related metabolites contributing the most. Furthermore, combined diagnostic models of charactered bacteria and metabolites answered well in the early, long-term, and dose-dependent responses for 131I therapy. CONCLUSIONS: Different stages of 131I therapy exert various effects on gut microecology, which play an essential role in regulating radiotoxicity and predicting the therapeutic response.

An age-and sex-matched postoperative therapy should be required in thyroid papillary carcinoma.

Background and purpose: Thyroid papillary carcinoma (PTC) had a high possibility of recurrence after surgery, and thyroid stimulating hormone (TSH) suppression and radioactive iodine (131I) were used for postoperative therapy. This study explored the potential mechanism of lymph node metastasis (LNM) and aimed to develop differentiated treatments for PTC. Method: This study explored the risk factors of lymph node metastasis in PTC by analyzing the clinical information of 2073 cases. The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) and the Gene Expression Omnibus (GEO) databases of gene expression were analyzed to identify the interrelationships between gene expression to phenotype. Results: Analyzing clinical data, we found that male gender, younger age, larger tumor size, and extra-thyroidal extension (ETE) were risk significant risk factors for lymph node metastasis(P<0.05). Conversely, thyroid function parameters such as TSH, FT3, FT4, TSH/FT3, and TSH/FT4 didn't correlate with LNM(P>0.05), and TSH levels were observed to be higher in females(P<0.05). Gene expression analysis revealed that SLC5A5 was down-regulated in males, younger individuals, and those with lymph node metastasis, and a lower level of SLC5A5 was associated with a worse disease-free survival(P<0.05). Additionally, our examination of single-cell RNA sequencing (scRNA-seq) data indicated that SLC5A5 expression was reduced in tumors and lymph node metastasis samples, correlating positively with the expression of TSHR. Conclusion: The impact of TSH on PTC behavior remained unclear, while the capacity for absorbing 131I in dependence on SLC5A5 showed variations across different genders and ages. We conclude that postoperative treatment of PTC should take into account the differences caused by gender and age.

Thyroid ultrasound findings in young and middle-aged adults living in the region of the Chornobyl Nuclear Power Plant.

Nearly forty years have passed since the Chornobyl Nuclear Power Plant accident, which resulted in childhood and adolescent thyroid cancers increasing due to internal exposure to iodine-131. Therefore, the Fukushima Daiichi Nuclear Power Station accident, in 2011, raised serious anxiety about potential risks of thyroid cancers. Considering the causal relationship between thyroid cancer and the Chornobyl accident, radiation dose to the thyroid due to this accident should be considered carefully. In addition, a thorough investigation of any influence of ultrasound screening of the thyroid on the detection of thyroid diseases was still missing. Consequently, from 2019 to 2021, the frequency of abnormal thyroid findings from screening of residents in Zhytomyr, Ukraine, which was heavily contaminated by the accident, was evaluated in this study. For this, the same diagnostic classification of any thyroid ultrasound findings as those of the Fukushima Health Management Survey were used. This classification used the categories "A1" (no findings), "A2" (thyroid cysts less than 20 mm and/or thyroid nodules less than 5 mm), and "B" (thyroid cysts more than 20 mm and/or thyroid nodules more than 5 mm). 2,978 participants were analyzed. It was found that the frequency of "B" findings increased with age. This may be due to the observed increased incidence of not only malignant but also benign thyroid nodules. It may well be that such an increase will also be observed in Fukushima in the future. It is concluded that future thyroid examiners in Fukushima should be aware of findings specific to adults, such as chronic thyroiditis. For comparison, it will be necessary to perform longitudinal studies in the Japanese population not exposed to radiation from the Fukushima accident.

Unusual Metastatic Sites and Radioiodine Uptake in Patients of Differentiated Thyroid Carcinoma with Atypical Clinical Presentations: Utilization of 131 I-Whole-Body Scintigraphy with Regional SPECT/CT.

Differentiated thyroid carcinoma (DTC) usually is slow growing and carries a good prognosis. It most commonly tends to spread locally to regional lymph nodes in 20 to 60% of patients. The presence of distant metastasis impacts overall survival and prognosis. The lungs, bones, and the brain are typically involved in distant sites with less common metastatic sites that include the liver, kidney, skeletal muscle, adrenal glands, bladder, and skin. These unusual sites are rare and pose a diagnostic challenge and impact clinical decision-making to a great extent. The radioiodine 131 I whole-body scintigraphy with single-photon emission computed tomography/computed tomography can provide a thorough investigation of unusual sites of uptake leading to diagnosis of these metastases. We present a case series of DTC showing unusual sites of metastasis and/or radioiodine uptake in urinary bladder, in the third metacarpal bone of left hand and lastly in the forearm at postoperative hypertrophic scar area.

Technical note: Quantifying radionuclide residues in hospital wastewater: A case study on [131I]I and [177mLu]Lu/[177Lu]Lu.

BACKGROUND: Historically, [131I]I has been a common isotope in radionuclide therapy, with [177Lu]Lu-labelled radiopharmaceuticals now seeing a surge in use. These can include no-carrier-added or carrier-added [177Lu]Lu with slight impurities of [177mLu]Lu with a significantly longer half-life than [131I]I. Wastewater from therapy wards can contain a mixture of these radioisotopes. In some countries, national regulations require wastewater to be stored in dedicated systems before it is discharged into the public sewage system. To fulfill legal requirements, the nuclide specific activity concentration must be verified. PURPOSE: We evaluate a method for determining the activity concentration of [177mLu]Lu /[177Lu]Lu at equilibrium and [131I]I in pure and mixed samples in order to prove that the determined values are reliably below the limits for release. METHODS: We analysed the emitted energy spectrum of 1 L samples with a wastewater counter using an energy window-based approach by evaluating measurements from two different time points. Based on the law of decay and the time and energy-dependent measured values, equation systems were set up to calculate the count rates for [131I]I and [177mLu]Lu, which were converted into activity concentration using calibration factors. RESULTS: There is strong linear correlation between the nominal and determined activity concentrations (correlation coefficients R = 0.99; coefficient of determinations R2 = 0.99). We underestimate the actual activity concentration by a median of -1.4% for [177mLu]Lu and overestimate the activity concentration for [131I]I by a median of 7.1%. CONCLUSION: We show that an undercut of the clearance levels for material release is measurable. We analyse and determine activity concentrations of mixed samples consisting of [131I]I and [177mLu]Lu/[177Lu]Lu in equilibrium. The method is simple to implement using a conventional wastewater counter, however with a slightly increased effort, as two samples and measurements are required. The methodology can be adapted for the analysis of other nuclide mixtures.

The Effect of 131I Therapy on the Eradication of Helicobacter pylori in Patients with Thyroid Disorders: A Preliminary Study.

The leading cause of gastritis and its complications is Helicobacter pylori Radioactive iodine (131I) accumulates significantly in the stomach after consumption. On this basis, we decided to determine whether different doses of 131I in the stomach would be effective in eradicating the infection. Methods: All patients with hyperthyroidism or differentiated thyroid carcinoma who were referred for 131I treatment were invited to the study. A stool antigen test was conducted before consumption of 131I (0.15-5.5 GBq) and was repeated 2 mo later to detect H. pylori infection. Results: H. pylori positivity was found in 51.8% (14/27) of the patients. At 2 mo after treatment, 13 of the 14 patients with differentiated thyroid carcinoma or hyperthyroidism who had been identified as positive for H. pylori stool antigen before 131I administration were still positive, representing a nonsignificant eradication rate of 7.1%. Conclusion: Administration of 131I to patients with H. pylori did not show potential to eliminate the infection.

Accuracy of patient-specific I-131 dosimetry using hybrid whole-body planar-SPECT/CT I-123 and I-131 imaging.

PURPOSE: This study aimed to assess the accuracy of patient-specific absorbed dose calculations for tumours and organs at risk in radiopharmaceutical therapy planning, utilizing hybrid planar-SPECT/CT imaging. METHODS: Three Monte Carlo (MC) simulated digital patient phantoms were created, with time-activity data for mIBG labelled to I-123 (LEHR and ME collimators) and I-131 (HE collimator). The study assessed the accuracy of the mean absorbed doses for I-131-mIBG therapy treatment planning. Multiple planar whole-body (WB) images were simulated (between 1 to 72 h post-injection (p.i)). The geometric-mean image of the anterior and posterior WB images was calculated, with scatter and attenuation corrections applied. Time-activity curves were created for regions of interest over the liver and two tumours (diameters: 3.0 cm and 5.0 cm) in the WB images. A corresponding SPECT study was simulated at 24 h p.i and reconstructed using the OS-EM algorithm, incorporating scatter, attenuation, collimator-detector response, septal scatter and penetration corrections. MC voxel-based absorbed dose rate calculations used two image sets, (i) the activity distribution represented by the SPECT images and (ii) the activity distribution from the SPECT images distributed uniformly within the volume of interest. Mean absorbed doses were calculated considering photon and charged particle emissions, and beta emissions only. True absorbed doses were calculated by MC voxel-based dosimetry of the known activity distributions for reference. RESULTS: Considering photon and charged particle emissions, mean absorbed dose accuracies across all three radionuclide-collimator combinations of 3.8 ± 5.5% and 0.1 ± 0.9% (liver), 5.2 ± 10.0% and 4.3 ± 1.7% (3.0 cm tumour) and 15.0 ± 5.8% and 2.6 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively. Considering charged particle emissions, accuracies of 2.7 ± 4.1% and 5.7 ± 0.7% (liver), 3.2 ± 10.2% and 9.1 ± 1.7% (3.0 cm tumour) and 13.6 ± 5.7% and 7.0 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively. CONCLUSION: The hybrid WB planar-SPECT/CT method proved accurate for I-131-mIBG dosimetry, suggesting its potential for personalized treatment planning.

Aurora Kinase A inhibition enhances DNA damage and tumor cell death with 131I-MIBG therapy in high-risk neuroblastoma.

BACKGROUND: Neuroblastoma is the most common extra-cranial pediatric solid tumor. 131I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical highly specific for neuroblastoma tumors, providing potent radiotherapy to widely metastatic disease. Aurora kinase A (AURKA) plays a role in mitosis and stabilization of the MYCN protein in neuroblastoma. We aimed to study the impact of AURKA inhibitors on DNA damage and tumor cell death in combination with 131I-MIBG therapy in a pre-clinical model of high-risk neuroblastoma. RESULTS: Using an in vivo model of high-risk neuroblastoma, we demonstrated a marked combinatorial effect of 131I-MIBG and alisertib on tumor growth. In MYCN amplified cell lines, the combination of radiation and an AURKA A inhibitor increased DNA damage and apoptosis and decreased MYCN protein levels. CONCLUSION: The combination of AURKA inhibition with 131I-MIBG treatment is active in resistant neuroblastoma models.

Radio theranostics in paragangliomas and pheochromocytomas.

This continuing education aims to present in a clear and easy-to-understand manner the biology of paragangliomas and pheochromocytomas (PPGLs), the functional imaging studies available for their diagnosis and therapeutic planning, the requirements necessary to administer radioligand therapy (RLT) and the characteristics of these treatments (inclusion criteria, administration protocols, adverse effects and future perspectives). In this pathology we have two RLT options: [131I]MIBG and [177Lu]Lu-DOTA-TATE. The indication for treatment is determined by the expression of its therapeutic target in functional imaging studies, allowing precision and personalized medicine. Although most of the results we have for both treatments have as origin small retrospective series, RLT is presented as a safe and well-tolerated therapeutic option in PPGLs with slow-moderate progression or with uncontrollable symptoms, obtaining high disease control rates.

Measurements of 131I activity in thyroid of workers at the place of radioiodine therapy in 38 hospitals in China.

To investigate the levels of 131I activity in thyroid of workers at the place of radioiodine therapy and their main influential factors in China, 341 workers at 38 hospitals performing radioiodine therapy procedure in five provinces were recruited to be measured in 2021. A hand-held gamma spectrometer with NaI(Tl) probe was plastered to the thyroids and thighs of the subjects during the measurement, and each measurement time was 120 s. The internal exposure dose was calculated, and the committed effective dose was estimated. In 86 (25.22%) of the 341 examined workers, 131I thyroid activity was above minimum detectable activity (MDA, 26.6 Bq). The maximum activity was 4.9 × 103 Bq. The detection results above MDA were at 22 (57.89%) different hospitals. The detectable rate for private hospitals (4.8%) was significantly lower than that for public hospitals (26.6%), P < 0.05. The detectable rate for hospitals in provincial capital cities (15.4%) was significantly lower than in nonprovincial capital cities (41.7%), P < 0.001. The detectable rate for hospitals engaged in 131I therapy for thyroid cancer (31.2%) was significantly higher than only for hyperthyroidism (10.3%), P < 0.001. A total of 32 subjects' committed effective dose might exceed 1 mSv. Results indicated the 131I activity in the thyroid of workers at the place of radioiodine varied considerably in China, and mainly related to ownership, location and therapy program of the hospitals.

Determination of Frequency of Type 2 Deiodinase Thr92Ala Polymorphism (rs225014) in 131I-treated Differentiated Thyroid Cancer Patients Undertaking L-thyroxine (L-T4) Suppression Therapy.

Introduction: Type 2 deiodinase (DIO2) enzyme plays a vital role in peripheral T4 to T3 conversion and in the negative feedback regulation of pituitary thyroid-stimulating hormone (TSH) secretion. Thr92Ala polymorphism (rs225014) is a common single-nucleotide polymorphism (SNP) that lowers DIO2 activity and is associated with diverse physiological disorders. Differentiated thyroid cancer (DTC) patients are given L-T4 therapy after total thyroidectomy and 131I treatment to suppress TSH levels. Aim: The aim of the study was to determine the frequency of rs225014 in DTC patients and to investigate its effect on the thyroid function tests (TFTs) and L-T4 dose required to suppress TSH levels. Materials and Methods: The study included a DTC patient group and a control group. TFTs were estimated by RIA/IRMA kits. Genomic DNA of all the subjects was screened for rs225014 SNP by polymerase chain reaction. Results: The frequency of Thr/Thr (wild type), Thr/Ala (heterozygous mutant), and Ala/Ala (homozygous mutant) genotypes in the DTC patients' group was 0.21, 0.52, and 0.27, respectively. T3 levels and T3/T4 ratio were significantly low in the Ala/Ala genotype in the DTC group indicating impaired DIO2 activity. L-T4 dose requirement to suppress TSH levels in the DTC patients harboring rs225014 SNP was not statistically different from the wild-type genotype. Conclusion: The SNP rs225014 was observed to be associated with T3 and T3/T4 ratio but not with the L-T4 dose in DTC harboring SNP suggesting the presence of a compensatory pathway to overcome DIO2 impairment. However, it is essential to study the genetic makeup of DTC patients showing reduced response to TSH suppression to enable quicker decision-making in the implementation of personalized L-T4 dose to prevent any adverse effects.

Disrupted gut microecology after high-dose 131I therapy and radioprotective effects of arachidonic acid supplementation.

BACKGROUND: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. METHODS: A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses. RESULTS: 131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1. CONCLUSION: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.

Approach to the Patient: Concept and Application of Targeted Radiotherapy in the Paraganglioma Patient.

Paragangliomas can metastasize, posing potential challenges both in symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and 177Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians' knowledge of the stepwise approach to treat these patients with paraganglioma-targeted radiotherapies. It comprehensively discusses current approaches to selecting paraganglioma patients for targeted radiotherapies and how to choose between the two radiotherapies based on specific patient and tumor characteristics, when either therapy is feasible, or one is superior to another. The safety, efficacy, toxicity profiles, and optimization of these radiotherapies are also discussed, along with other therapeutic options including radiotherapies, available for patients besides these two therapies. Perspectives in radiotherapies of paraganglioma patients are outlined since they hold promising approaches in the near future that can improve patient outcomes.

Standard therapy or additionally radioactive iodine (131I) therapy; which will stop the recurrence of glioblastoma multiforme (GBM)?

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Authors of the article pose a direct question: Is it possible to treat GBM solely with radioactive iodine (¹³¹I) therapy without employing the sodium iodide symporter (NIS) gene? After all, NIS has been detected not only in the thyroid but also in various tumours. The main author of this article (A.C.), with the assistance of her colleagues (physicians and pharmacologists), underwent ¹³¹I therapy after prior iodine inhibition, resulting in approximately 30% reduction in tumour size as revealed by magnetic resonance imaging (MRI). Classical therapy for GBM encompasses neurosurgery, conventional radiotherapy, and chemotherapy (e.g. temozolomide). Currently, tyrosine kinase inhibitors (imatinib, sunitinib, and sorafenib) are being used. Additionally, novel drugs such as crizotinib, entrectinib, or larotrectinib are being applied. Recently, personalised multimodal immunotherapy (IMI) based on anti-tumour vaccines derived from oncolytic viruses has been developed, concomitant with the advancement of cellular and molecular immunology. Thus, ¹³¹I therapy has been successfully employed for the first time in the case of GBM recurrence.

Synthesis, Screening, and Evaluation of Theranostic Molecular CPCR4-Based Probe Targeting CXCR4.

Chemokines and chemokine receptors are indispensable to play a key role in the development of malignant tumors. As one of the most widely expressed chemokine receptors, chemokine (C-X-C motif) receptor 4 (CXCR4) has been a popular research focus. In most tumors, CXCR4 expression is significantly upregulated. Moreover, integrated nuclide diagnosis and therapy targeting CXCR4 show great potential. [68Ga]Ga-pentixafor, a radioligand targeting CXCR4, exhibits a strong affinity for CXCR4 both in vivo and in vitro. However, [177Lu]Lu-pentixather, the therapeutic companion of [68Ga]Ga-pentixafor, requires significant refinement to mitigate its pronounced hepatic biodistribution. The objective of this study was to synthesize theranostic molecular tracers with superior CXCR4 targeting functions. The Daudi cell line, which highly expressed CXCR4, and the MM.1S cell line, which weakly expressed CXCR4, were used in this study. Based on the pharmacophore cyclo (-d-Tyr-n-me-d-Orn-l-Arg-L-2-NAL-Gly-) (CPCR4) of pentixafor, six tracers were synthesized: [124I]I-1 ([124I]I-CPCR4), [99mTc]Tc-2 ([99mTc]Tc-HYNIC-CPCR4), [124I]I-3 ([124I]I-pentixafor), [18F]AlF-4 ([18F]AlF-NETA-CPCR4), [99mTc]Tc-5 ([99mTc]Tc-MAG3-CPCR4) and [124I]I-6 ([124I]I-pentixafor-Ga) and their radiochemical purities were all higher than 95%. After positron emission tomography (PET)/single-photon emission computed tomography (SPECT) imaging, the [124I]I-6 group exhibited the best target-nontarget ratio. At the same time, comparing the [68Ga]Ga-pentixafor group with the [124I]I-6 group, we found that the [124I]I-6 group had a better target-nontarget ratio and lower uptake in nontarget organs. Therefore, compound 6 was selected for therapeutic radionuclide (131I) labeling, and the tumor-bearing animal models were treated with [131I]I-6. The volume of the tumor site was significantly reduced in the treatment group compared with the control group, and no significant side effects were found. [124I]I-6 and [131I]I-6 showed excellent affinity for targeting CXCR4, and they showed great potential for the integrated diagnosis and treatment of tumors with high CXCR4 expression.

Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1alpha After Treatment: A Cell Regulation Study / Observación del Efecto Clínico de Apatinib Combinado con 131I para el Cáncer de Tiroides Diferenciado Resistente al Yodo Radiactivo y Análisis de Importancia Pronóstica de la Proteína Inflamatoria 1alfa de Macrófagos Después del Tratamiento: Un Estudio de Regulación Celular

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.