Search

Background: 124-iodine ( 124 I) is used for positron emission tomography (PET) diagnostics and therapy planning in patients with differentiated thyroid cancer (DTC). Small lesion sizes (<10 mm) and low 124 I uptake are challenging conditions for the detection of DTC lymph node lesions., Purpose: The aim of this study was to systematically investigate the lesion detectability and quantification performance under clinically challenging imaging conditions using non-time-of-flight (TOF) PET/magnetic resonance imaging (MRI) in the clinical context of radionuclide therapy planning of DTC patients., Methods: PET/MR measurements were performed on the Siemens Biograph mMR using a small lesion NEMA-like phantom (six glass spheres, diameters 3.7-9.7 mm). 60 min list-mode data were acquired for nine activity concentrations (AC) ranging from 25 kBq/mL to 0.25 kBq/mL using a sphere-to-background ratio of 20:1. PET list-mode data were divided into five timeframes (60, 30, 16, 8, and 4 min) and reconstructed using either ordered-subsets expectation maximization (OSEM) or OSEM+ point spread function (PSF) algorithm. For all reconstructions, the smallest detectable sphere size was investigated in a human observer study. Partial volume effect (PVE) corrected PET images (contour and oversize-based approach) were analyzed considering a ± 30% deviation range between imaged and true AC as acceptable. Clinical data of eight DTC patients with small lymph node lesions were evaluated to assess agreement between the PVE correction approaches., Results: Longer PET acquisition times, higher ACs, and PSF reconstructions resulted in improved PET image quality and overall improved lesion detectability. The smallest 3.7 mm sphere was only visible under the best imaging conditions. Using a typical clinical 124 I whole-body PET/MRI protocol with an acquisition time of 8 min using OSEM reconstructions, all lesions of ≥ 6.5 mm in diameter could be detected and the quantification provided reliable results approximately above 5.0 kBq/mL. An accurate quantification of ACs in the 4.8 mm sphere was not feasible in this study. In the clinical evaluation of 10 lesions, a good agreement between oversize- and contour-based PVE corrections was observed (<15% deviation)., Conclusions: The results showed that a reliable quantification of 124 I uptake with PET/MRI is feasible and, therefore, could be used to perform radioiodine pre-therapy lesion dosimetry and individualized therapy planning in DTC patients., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

This study aimed to establish and validate prognostic nomogram models for patients who underwent 131 I therapy for thyroid cancer with distant metastases. The cohort was divided into training (70%) and validation (30%) sets for nomogram development. Univariate and multivariate Cox regression analyses were used to identify independent predictors for overall survival (OS) and progression-free survival (PFS). Nomograms were developed based on these predictors, and Kaplan-Meier curves were constructed for validation. Among 451 patients who were screened, 412 met the inclusion criteria and were followed-up for a median duration of 65.2 months. The training and validation sets included 288 and 124 patients, respectively. Pathological type, first 131 I administrated activity, and lesion 131 I uptake in lesions were independent predictors for PFS. For OS, predictors included gender, age, metastasis site, first 131 I administrated activity, 131 I uptake, pulmonary lesion size, and stimulated thyroglobulin levels. These predictors were used to construct nomograms for predicting PFS and OS. Low-risk patients had significantly longer PFS and OS compared to high-risk patients, with 10-year PFS rates of 81.1% vs. 51.9% and 10-year OS rates of 86.2% vs. 37.4%. These may aid individualized prognostic assessment and clinical decision-making, especially in determining the prescribed activity for the first 131 I treatment., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics declarations: The Ethics Committee of Zhejiang Cancer Hospital provided ethical approval for this study (IRB-2024-53) and waived the requirement for individual written informed consent for this retrospective analysis. The study was conducted in accordance with the principles of the Declaration of Helsinki., (© 2025. The Author(s).)

About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53 R175H (p53 R172H in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53 R175H could prove immensely value. We aimed to evaluate the in vitro and in vivo binding properties of two novel anti-p53 R175H monoclonal antibodies and to assess their performance as agents for molecular imaging. In vitro, 125 I-4H5 and 125 I-7B9 demonstrated long shelf life and antigen-specific binding. Our in vivo study design allowed head-to-head comparison of the antibodies in a double tumor model using repeated SPECT/CT imaging, followed by biodistribution and autoradiography. Both tracers performed similarly, with marginally faster blood clearance for 125 I-7B9. Repeated molecular imaging demonstrated suitable imaging characteristics for both antibodies, with the best contrast images occurring at 48 h post-injection. Significantly higher uptake was detected in the mut-p53-expressing tumors, confirmed by ex vivo autoradiography. We conclude that molecular imaging with an anti-p53 R175H tracer could be a promising approach for cancer diagnostics and could be further applied for patient stratification and treatment response monitoring of mutant p53-targeted therapeutics., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Targeted radionuclide therapy (TRT) is a cancer treatment with relative therapeutic efficacy across various cancer types. We studied the therapeutic potential of TRT using fibroblast activation protein-α (FAP) targeting sdAbs (4AH29) labelled with 225 Ac or 131 I in immunocompetent mice in a human FAP (hFAP) expressing lung cancer mouse model. We further explored the combination of TRT with programmed cell death ligand 1 (PD-L1) immune checkpoint blockade (ICB)., Methods: We studied the biodistribution and tumour uptake of [ 131 I]I-GMIB-4AH29 and [ 225 Ac]Ac-DOTA-4AH29 by ex vivo γ-counting. Therapeutic efficacy of [ 131 I]I-GMIB-4AH29 and [ 225 Ac]Ac-DOTA-4AH29 was evaluated in an immunocompetent mouse model. Flow cytometry analysis of tumours from [ 225 Ac]Ac-DOTA-4AH29 treated mice was performed. Treatment with [ 225 Ac]Ac-DOTA-4AH29 was repeated in combination with PD-L1 ICB., Results: The biodistribution showed high tumour uptake of [ 131 I]I-GMIB-4AH29 with 3.5 ± 0.5% IA/g 1 h post-injection (p.i.) decreasing to 0.9 ± 0.1% IA/g after 24 h. Tumour uptake of [ 225 Ac]Ac-DOTA-4AH29 was also relevant with 2.1 ± 0.5% IA/g 1 h p.i. with a less steep decrease to 1.7 ± 0.2% IA/g after 24 h. Survival was significantly improved after treatment with low and high doses [ 131 I]I-GMIB-4AH29 or [ 225 Ac]Ac-DOTA-4AH29 compared to vehicle solution. Moreover, we observed significantly higher PD-L1 expression in tumours of mice treated with [ 225 Ac]Ac-DOTA-4AH29 compared to vehicle solution. Therefore, we combined high dose [ 225 Ac]Ac-DOTA-4AH29 with PD-L1 ICB showing therapeutic synergy., Conclusion: [ 225 Ac]Ac-DOTA-4AH29 and [ 131 I]I-GMIB-4AH29 exhibit high and persistent tumour targeting, translating into prolonged survival in mice bearing aggressive tumours. Moreover, we demonstrate that the combination of PD-L1 ICB with [ 225 Ac]Ac-DOTA-4AH29 TRT enhances its therapeutic efficacy., Competing Interests: Declarations. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the ethics committee for use of laboratory animals of the Vrije Universiteit Brussel (ethical dossier numbers: 22-272-12, 22-272-19, 23-214-12). Competing interests: K.B., N.D., M.D., M.K. and T.L have patents on using sdAbs for imaging and therapy. T.L., N.D. and M.K. have ownership in AbScint. M.K. received research funding from Precirix. N.D. and M.D are respectively consultant and employee for and hold ownership in Precirix. A.R.P.A., L.N., M.B. and S.N. are employees of Precirix. M.K. is an editor of EJNMMI., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: A 20-year-old man with papillary thyroid cancer received a fourth radioiodine regimen to treat 131 I-avid lung metastases. Posttherapeutic whole-body scan revealed focal radioiodine uptake on the anterior region of the left lower limb that was not visible on previous whole-body scan and which suggested skin contamination. Visual examination of the left leg evidenced a posttraumatic scab caused by a fall 2 weeks before. Skin metastasis was ruled out. 131 I SPECT/CT acquisition ruled out bony uptake and confirmed that the skin uptake was related to the superficial scab., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 23-year-old woman underwent a near-total thyroidectomy approximately 4 months prior due to papillary carcinoma. To eliminate residual thyroid tissue, she was administered 130 mCi of 131I during her initial radioiodine therapy session. After receiving therapy for 3 days, a focus of radioiodine uptake was noted in the left pelvic cavity on the posttherapy 131I whole-body image. Further analysis using SPECT/CT imaging pinpointed the uptake to the left ovary. Histopathological findings confirmed the presence of a mature teratoma in the ovary., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Here, we have compiled all key statements derived from these guidelines and delved into details on which scenarios the diagnostic whole-body iodine scan (DxWBIS) might be useful., Methods: We identified all relevant guidelines by searching the MEDLINE/PubMed databases, Google Scholar, and Ovid from 2006 onwards using keywords related to DxWBIS, RxWBIS, iodine scintigraphy, and iodine scan. We excluded case reports/series, original articles, and clinical trials while including guidelines or consensus opinions. Additionally, we reviewed existing literature to ensure no guidelines were overlooked., Results: Overall, 23 relevant guidelines or consensus opinions discussed their views on the role of DxWBIS. Different indications for DxWBIS have been largely discussed in the last few years. However, the role of DxWBIS has been well established after treatment with 131I, with still limited evidence in the other clinical assessments., Conclusions: Most guidelines find DxWBIS appealing for higher-risk patients, particularly those with a chance of recurrence; additional well-designed studies are required to address further indications., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction/objective: Active moderate-to-severe thyroid eye disease (TED) is a major therapeutic challenge. Pulse therapy with intravenous glucocorticoids is the standard treatment, with variable response. Radioactive iodine therapy (RAI) was reported as a risk factor for onset or worsening of TED. We evaluated putative predictive factors for response to intravenous methylprednisolone in patients with active TED., Methods: Data were collected for 64 consecutive patients (45 women) with active moderate-to-severe TED treated with a minimum cumulative dose of 4.5g methylprednisolone. Patients were classified as responders (R) or non-responders (NR) on Clinical Activity Score (CAS), and clinical features were compared between groups., Results: Sixty-two patients had Graves' disease (GD), and 2 had Hashimoto's thyroiditis (HT). Median age at thyroid dysfunction diagnosis, TED manifestation and pulse therapy was 46, 48 and 51 years, respectively; 56.2% were euthyroid when TED manifested. Among them, 73.4% were responders. R and NR were comparable for gender, age, thyroid function, serum antibodies, disease duration, pre-treatment CAS, smoking, lipid profile, and adverse events. Forty-nine patients were treated with RAI for GD: 15 before the active phase of TED (before pulse therapy), 16 during, 17 after, and 1 both before and after pulse therapy. Response rate was higher in patients who received RAI during than after pulse therapy (P=0.032) and similar to those not treated with RAI at all (P=0,599)., Conclusion: Pulse therapy was effective in the majority of patients. The only factor associated with response to pulse therapy was the timing of RAI, suggesting that it seems to be safe when used concomitantly with pulse therapy., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Non-invasive determination of amyloid-β peptide (Aβ) and tau deposition are important for early diagnosis and therapeutic intervention for Alzheimer's disease (AD) and non-AD tauopathies. In the present study, we investigated the capacity of a novel radioiodinated compound AD-DRK ( 123/125 I-AD-DRK) with 50% inhibitory concentrations of 11 nM and 2 nM for Aβ and tau aggregates, respectively, as a single photon emission computed tomography (SPECT) ligand in living brains. In vitro and ex vivo autoradiography with 125 I-AD-DRK was performed in postmortem human and two transgenic (Tg) mice lines with either fibrillar Aβ or tau accumulation, APP23 and rTg4510 mice. SPECT imaging of 123 I-AD-DRK was performed in APP23 mice to investigate the ability of AD-DRK to visualize fibrillar protein deposition in the living brain. In-vitro autoradiogram of 125 I-AD-DRK showed high specific radioactivity accumulation in the temporal cortex and hippocampus of AD patients and the motor cortex of progressive supranuclear palsy (PSP) patients enriched by Aβ and/or tau aggregates. Ex-vivo autoradiographic images also demonstrated a significant increase in 125 I-AD-DRK binding in the forebrain of both APP23 and rTg450 mice compared to their corresponding non-Tg littermates. SPECT imaging successfully captured Aβ deposition in the living brain of aged APP23 mice. The present study developed a novel high-contrast SPECT agent for assisting the diagnosis of AD and non-AD tauopathies, likely benefiting from its affinity for both fibrillar Aβ and tau., Competing Interests: Declaration of competing interest Shanghai Fuji Medical Technology Co. LTD hold patents on compounds related to the present report (JP6831802/KR10–2,428,569). The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Hepatocellular carcinoma (HCC) is a common cause of cancer‑related mortality and morbidity worldwide. While iodine‑125 ( 125 I) particle brachytherapy has been extensively used in the clinical treatment of various types of cancer, the precise mechanism underlying its effectiveness in treating HCC remains unclear. In the present study, MHCC‑97H cells were treated with 125 I, after which, cell viability and proliferation were assessed using Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine and colony formation assays, cell invasion and migration were evaluated using wound healing and Transwell assays, and cell apoptosis was determined using flow cytometry. Omics data were analyzed using Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and STRING analyses to observe the key genes that exhibited significant changes at the transcriptional and protein levels in MHCC‑97H cells treated with 125 I particles. Finally, the expression levels of key genes (GPNMB, C4BPA, CTH, H1‑0 and MT2A) were verified through reverse transcription quantitative PCR. Following treatment with 125 I, the proliferation, invasion and migration of MHCC‑97H cells were inhibited, and apoptosis was enhanced. The results of omics data analysis indicated that the biological behavior of MHCC‑97H cells treated with 125 I was related to the expression levels of CTH and MT2A genes. These findings indicated that intervention with 125 I radiation particles may induce changes in gene expression, potentially influencing alterations in biological characteristics. In conclusion, these insights may shed light on the underlying mechanisms of 125 I radiation particle therapy in HCC and offer novel targets for HCC treatment.

Radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) accounts for the vast majority of thyroid-related mortality and, until recently, there were limited preclinical models for iodine uptake prediction. In the current study, we aim to establish a primary tumor-derived organoid model of DTC and predict radioiodine (RAI) uptake of tumor residue. The genotypic and phenotypic features between organoid and parental tissue were compared. The RAI uptake assay was used to evaluate the organoid's RAI uptake capacity, and related patients' RAI whole-body scans were used to verify the assay's predictive sensitivity. A total of 20 patient-derived DTC organoids have been established. Whole-exome sequencing and immunofluorescence analysis demonstrated that organoids faithfully recapitulated main features of the original tumor tissue. RAI-avid organoids (n = 11) presented significantly higher RAI uptake than the RAI-refractory (RAI-R) group (n = 9; 384.4 ± 102.7 vs 54.2 ± 13.2 cpm/105 cells, P < .0001). A threshold value in organoids of less than 250 cpm/105 cell was found to have a predictive sensitivity of 95.0% for distinguishing RAI-R from RAI-avid patients when paired to clinical information. Notably, we found that several tyrosine kinase inhibitors moderately re-sensitize iodine uptake by using organoids derived from 3 patients with different genetic mutation backgrounds. In conclusion, patient-derived DTC organoids recapitulated the main characteristics of their parental tissues and preserved ability to uptake radioiodine, showing potential in the development of novel drugs to boost iodine avidity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

A fire in one of the Windscale nuclear reactors at Sellafield (Cumbria, England) in October 1957 released 1,800 TBq of 131 I (half-life, 8 days) to atmosphere. Measurements of 131 I 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 131 I 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 131 I. Three areas of Cumbria with different 131 I 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 131 I 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 131 I 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 131 I, such as occurred following the Fukushima nuclear accident in 2011., Competing Interests: Declarations. Ethics approval and consent to participate: Permission for the study was given on 30 July 2018 by the Newcastle University, Faculty of Medical Sciences Research Ethics Committee (application number: 1530/6677/2018). Approval from the Public Benefit and Privacy Panel for Health and Social Care (reference number 1718 − 0248) was received on 19 March 2019. Data Sharing Agreement (GDPR Compliant) between Public Health England, an executive agency of the Department of Health and Social Care, and the University of Newcastle upon Tyne, dated 9 September 2019. Consent for publication: Not applicable. Competing interests: R.W. is a member of the Technical Working Party of the Compensation Scheme for Radiation-Linked Diseases (http://www.csrld.org.uk). Otherwise, the authors declare no potential conflict of interest., (© 2024. The Author(s).)

Purpose: PSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [ 123 I]I-PSMA-7. First, we hope that [ 123 I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa., Methods: We synthesized a high-affinity probe, [ 123 I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [ 123 I]I-PSMA-7 for detecting PCa., Results: Animal experiments verified the safety, targeting and effectiveness of [ 123 I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [ 123 I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging., Conclusion: With the aid of [ 123 I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [ 123 I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results., Trial Registration: Chinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023., (© 2024. The Author(s).)

Papillary thyroid cancer is associated with lymph node metastasis and tumor recurrence that need repeated surgery, entailing surgical challenges with a high risk of complications such as nerve damage and bleeding. Magseed is a metal coil used to detect non-palpable lesions and is an established modality in breast cancer surgery. In this case series, we explore the feasibility of Magseed in metastasis surgery of papillary thyroid cancer. Under the guidance of ultrasonography, Magseed is injected into the target tissue and intraoperatively detected with a handheld magnetometer probe, Sentimag®. Five patients with recurrence of papillary thyroid cancer were operated on with focused Magseed-guided localization. All patients had repeated surgery and radioiodine treatments. Four of the patients had lymph node metastasis hidden in the fibrosis, and one patient had recurrent tumor tissue on the left side of the larynx. Magseed was easy to use, safe, and precise in detecting the target tissue., Competing Interests: Declaration of competing interest All authors do not have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Abstract: Abnormal focal accumulation of 131 I is generally a reliable indicator of differentiated thyroid cancer metastases. However, many examples of false-positive 131 I uptake were reported, some of them of unusual nature. We report a case of 32-year-old man with differentiated thyroid cancer who underwent thyroid remnants ablation with radioiodine. An area of considerable 131 I uptake projecting onto lateral cervical areas was detected on posttherapy planar whole-body scan. Neck SPECT/CT scan was done to elucidate localization of the uptake, and activity was found in the patient's beard., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Alpha-mangostin (AM), the most representative xanthone derivative isolated from the rind of the Purple Mangosteen (Garcinia mangostana Linn), has been reported pharmacologically to be associated with breast cancer in silico, in vitro, and in vivo. Although the pharmacological effects of AM are believed to involve the estrogen receptor alpha (ERα), there are no reports available in the literature describing the binding of AM to ERα., Methods: In this study, iodine-125 ( 125 I)-labeled AM ([ 125 I]I-AM) was prepared, and its binding to ERα was investigated in vitro using MCF-7 cell lines. To investigate the applicability of radioiodine-labeled AM as a radiopharmaceutical for breast cancer, [ 125 I]I-AM was injected into nude mice bearing MCF-7., Results: The results obtained showed that the uptake of [ 125 I]I-AM into MCF-7 cells was found to be inhibited by AM and tamoxifen, suggesting that its uptake is partially mediated by ERα. In addition, the biodistribution studies using MCF-7 bearing nude mice showed that [ 125 I]I-AM accumulated in tumor tissues, although deiodination did occur, reducing the concentration of iodine-125 ( 125 I) in the targeted cells., Conclusion: These results suggested that AM would be a useful platform for the development of a new radiopharmaceutical targeting ERα. Further studies are, however, required to reduce deiodination of [ 125 I]I-AM in vivo., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Muchtaridi et al.)

This study evaluates the efficacy of [ 131 I]I-ERIC1 in targeting and inhibiting the growth of SCLC tumors in mice, focusing on tumor accumulation and regression and potential side effects. NCAM-positive NCI-H69 SCLC cells were implanted in CB 17 SCID mice, and [ 131 I]I-ERIC1 biokinetics were measured in organs and tissues at four post-injection time points (24, 72, 96, and 120 h). The experimental series compared tumor growth, survival, and changes in blood counts among three treatment groups (1, 2, or 3 MBq) and a control group, with treatments initiated either two or five days post implantation. [ 131 I]I-ERIC1 was synthesized with >95% radiochemical purity and a specific activity of 15 TBq/mmol. Tumor activity peaked at 31.5 ± 6.6% ID/g after four days, demonstrating significant antitumor efficacy, which resulted in sustained remission and extended survival. Hematological toxicity was observed, with the optimal dose identified as 2 MBq per animal administered two days post implantation. [ 131 I]I-ERIC1 shows promise as a theranostic agent for personalized cancer treatment by effectively targeting SCLC tumors with manageable side effects. However, further studies are required to optimize dosing strategies and minimize toxicity., Competing Interests: The authors declare no conflict of interest.

Radiolabelled autologous leukocytes have been used for the clinical diagnosis of inflammation and infection. To develop a stable and efficient radiopharmaceutical for labelling leukocytes, we prepared a novel radioiodinated cell-penetrating peptide, 125 I-TAT, using a bi-functional linker. 125 I-TAT was stable for two days under three different temperature conditions of -20 °C, 4 °C, and 40 °C, with its radiochemical purity remaining over 99%. Iodinated TAT was non-toxic to leukocytes with an IC 50 value of over 100 μM. The labelling efficiency of 125 I-TAT using 1ｘ10 7  cells ranged from 27% to 53% when the three leukocyte cell lines were pre-treated with DMSO. This is comparable to the labelling efficiency recommended by the guideline for conventional labelling agents using 2ｘ10 8  cells. Radioiodinated cell-penetrating peptide may be an improved radiopharmaceutical for white blood cell scans by further optimization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study compared a multimodal image-guided robot and three-dimensionally (3D) printed templates for implanting iodine-125 (I 125 ) radioactive seeds in patients with malignant tumours in the skull base and deep facial region. Seventeen patients who underwent I 125 radioactive seed implantation between December 2018 and December 2019 were included. The operation time, intraoperative blood loss, and accuracy of seed implantation were compared between the multimodal image-guided robot-assisted implantation (experimental) group (n = 7) and 3D-printed template-assisted implantation (control) group (n = 10). In total, 291 seeds were implanted in the experimental group and 436 in the control group; the mean error of seed implantation accuracy was 1.95 ± 0.13 mm and 1.90 ± 0.08 mm, respectively (P = 0.309). The preparation time was 26.13 ± 5.28 min in the experimental group and 0 min in the control group, while the average operation time was 34.44 ± 6.39 min versus 43.70 ± 6.06 min, respectively. The intraoperative blood loss was 4.96 ± 1.76 ml (experimental) versus 8.97 ± 2.99 ml (control) (P = 0.123). Multimodal image-guided robot-assisted I 125 radioactive seed implantation met the clinical requirements for treating malignant tumours in the skull base and deep facial regions., Competing Interests: Competing interests None., (Copyright © 2024 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

In the last three decades, an increase in thyroid cancer incidence has been observed worldwide, as well as in Lithuania. Although the rise was linked to overdiagnosis, the role of lifestyle and environmental factors, including exposure to ionizing radiation, cannot be excluded. In our retrospective study, we aimed to assess the association between the average age-specific thyroid dose due to the radioactive iodine uptake during childhood and adolescence from the Chernobyl fallout in Lithuania, and the trends of incidence of thyroid cancer from 1991 to 2015 in different regions. Averaged age-dependent thyroid doses were estimated for every municipality based on radioiodine activity in milk, reconstructed from available 131 I activity measurements in the grass. Thyroid cancer incidence rates were calculated for the entire population and for two age at the time of exposure groups: 0-19 years and 0-9 years. Thyroid cancer relative risk (RR) was estimated for three municipality-specific thyroid dose (for 0-year-old babies) categories: less than 100 mGy (reference group), 100-199 mGy, and ≥200 mGy. Over the study period (1991-2015), a total of 5664 cases of thyroid cancer were registered in the entire Lithuanian population; 817 cases in the age group from 0 to 19 years at the time of the Chernobyl accident, and 266 cases in the age group from 0 to 9 years. Age-standardized thyroid cancer incidence rates have notably increased since 2000, peaked in 2009 (especially in females), and then slightly decreased and stabilized. The estimated average municipality-specific age-dependent thyroid doses ranged from 270 mGy in western Lithuania to 1.5 mGy in central and northern Lithuania. For the age group of 0-19 years at the time of the accident, in the period 1991-1995, the thyroid cancer relative risk was significantly increased (RR 3.91; 95 % CI: 1.27-10.29, p=0.01) in the highest dose category, compared to the lowest (although based on a small number of cases). For the age group 0-9 years at the time of the accident, a tendency of increased RR in the highest dose category appeared in the most recent period, 2011-2015. Our observations need to be confirmed by further following trends of thyroid cancer incidence in the cohort of 0-19-year-old Lithuanians at the time of the Chernobyl accident., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Several case reports and a few studies have reported that hypothyroid patients have elevated serum potassium levels. However, hypothyroidism has not been widely accepted as a cause of hyperkalemia., Objectives: This study aims to evaluate the incidence of hyperkalemia and factors influencing serum potassium levels in thyroid cancer patients with hypothyroidism during thyroid hormone withdrawal before radioactive iodine (RAI) treatment., Methods: We conducted a retrospective review of electronic medical records from January 2017 to June 2021, involving 956 thyroid cancer patients post-thyroidectomy and undergoing RAI. Laboratory parameters, including serum potassium levels, were collected in both euthyroid (<1 year prior to RAI) and hypothyroid states., Results: Among 508 patients (mean age 52 years, 79.3% female), hyperkalemia (potassium ⩾ 5.0 mEq/L) occurred in 2.8%, without severe hyperkalemia (potassium ⩾ 6.5 mEq/L). The hypothyroid state exhibited significantly higher serum potassium than the euthyroid state [4.16 (IQR, 3.94-4.41) vs 4.10 (IQR, 3.90-4.35) mEq/L, P  < .01]. The mean change in potassium levels between the euthyroid and hypothyroid state was 0.05 ± 0.17 mEq/L. Pre-thyroid hormone withdrawal (euthyroid state) factors associated with serum potassium levels in the hypothyroid state included age, use of angiotensin-converting enzyme inhibitors, diabetes mellitus, serum BUN/creatinine, serum potassium levels, hemoglobin A1c (positive correlation); and thiazide use and eGFR (negative correlation). In the hypothyroid state, hyperkalemia was more likely in patients with serum potassium ⩾4.2 mEq/L (OR 9.36, P  < .01) or free T4 ⩾1.38 ng/dL (OR 7.05, P  < .01) during the euthyroid state., Conclusions: The incidence of hyperkalemia was low in our hypothyroid cohorts. However, physicians should remain vigilant for cases with risk factors for developing hyperkalemia., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Simultaneous imaging of the SPECT tracer 131 I and PET tracer 18 F is important in the diagnosis of high- and low-grade thyroid cancers because high-grade thyroid cancers have high 18 F-FDG and low 131 I uptake, while low-grade thyroid cancers have high 131 I and low 18 F-FDG uptake. In this study, Na 131 I and 18 F-FDG were simultaneously imaged using the Compton-PET system, in vivo. The angular resolution and sensitivity of the Compton camera with 356 keV gamma ray measured using a 133 Ba point source were 12.3° and 2 × 10 -5 , respectively. The spatial resolution and sensitivity of PET were measured with a 22 Na point source. The transaxial and axial spatial resolutions of the PET at the center of the FOV were 1.15 mm and 2.04 mm, respectively. Its sensitivity was 1.2 × 10 -4 . In-vivo images of the 18 F and 131 I isotopes were simultaneously acquired from mice. These showed that 18 F-FDG was active in the heart, brown fat, and brain, while Na 131 I was active in the thyroid, stomach, and bladder. Artifacts were found in the Compton camera images when the activity of 131 I was much lower than that of 18 F. This study demonstrates the potential of simultaneous clinical imaging of 18 F and 131 I., (© 2024. The Author(s).)

Diffuse intrinsic pontine glioma (DIPG) is a rare childhood malignancy with poor prognosis. There are no effective treatment options other than external beam therapy. We conducted a pilot, first-in-human study using 124 I-omburtamab imaging and theranostics as a therapeutic approach using a localized convection-enhanced delivery (CED) technique for administering radiolabeled antibody. We report the detailed pharmacokinetics and dosimetry results of intratumoral delivery of 124 I-omburtamab. Methods: Forty-five DIPG patients who received 9.0-370.7 MBq of 124 I-omburtamab intratumorally via CED underwent serial brain and whole-body PET/CT imaging at 3-5 time points after injection within 4, 24-48, 72-96, 120-144, and 168-240 h from the end of infusion. Serial blood samples were obtained for kinetic analysis. Whole-body, blood, lesion, and normal-tissue activities were measured, kinetic parameters (uptake and clearance half-life times) estimated, and radiation-absorbed doses calculated using the OLINDA software program. Results: All patients showed prominent activity within the lesion that was retained over several days and was detectable up to the last time point of imaging, with a mean 124 I residence time in the lesion of 24.9 h and dose equivalent of 353 ± 181 mSv/MBq. Whole-body doses were low, with a dose equivalent of 0.69 ± 0.28 mSv/MBq. Systemic distribution and activities in normal organs and blood were low. Radiation dose to blood was very low, with a mean value of 0.27 ± 0.21 mGy/MBq. Whole-body clearance was monoexponential with a mean biologic half-life of 62.7 h and an effective half-life of 37.9 h. Blood clearance was biexponential, with a mean biologic half-life of 22.2 h for the rapid α phase and 155 h for the slower β phase. Conclusion: Intratumoral CED of 124 I-omburtamab is a novel theranostics approach in DIPG. It allows for delivery of high radiation doses to the DIPG lesions, with high lesion activities and low systemic activities and high tumor-to-normal-tissue ratios and achieving a wide safety margin. Imaging of the actual therapeutic administration of 124 I-omburtamab allows for direct estimation of the therapeutic lesion and normal-tissue-absorbed doses., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Radioimmunotherapy (RIT) is a novel and promising cancer treatment method, with ongoing research focusing on RIT antibody selection, radionuclides, treatment options, and benefited patient groups. As we dive into the mechanisms of tumor biology, a deeper exploration of how RIT affects tumor tissue is needed to provide new ways to improve clinical treatment outcome and patient prognosis. We labeled the anti-PD-L1 monoclonal antibody atezolizumab with iodine-131 ( 131 I), separated and purified the labeled mAb with Sephadex G-25 medium gel filtration resin, and tested product stability. We detected the in vivo activity of 131 I-PD-L1 mAb by analyzing its in vivo biodistribution and performing SPECT imaging and then set different treatment groups to study the effect of 131 I-atezolizumab on the survival of tumor-bearing mice. Western blot, real-time quantitative PCR, and immunohistochemistry were used to detect the expression level of Caspase8 and Nlrp3 in tumor. TUNEL fluorescence staining was used to detect the apoptosis in the tumor. The radiopharmaceutical molecular probe 131 I-atezolizumab showed high stability and in vivo biological activity. The treatment regimen adopted had a positive effect on the survival of tumor-bearing mice. 131 I internal irradiation upregulated Caspase8 in tumor and ultimately inhibited solid tumor growth by activating apoptosis pathways. We also found a significant increase in the expression of NLRP3, which plays an important role in the pyroptosis pathway, in tumor. In summary, our data demonstrated that radiopharmaceuticals combined with immunotherapy affected tumor tissue by modulating relevant biological pathways, thereby achieving better antitumor effects compared with single therapy and providing new insights for promoting better patient prognosis and combination treatment strategies.

Purpose: To quantify changes in prostate size and seed movement over time after transperineal implantation of stranded 125 I seeds, and to determine their impact on prostate dosimetry., Methods: CT and MR (T2, balanced steady-state free precession) image triplets were acquired on days 0, 3, 10, and 30 for a cohort of 20 patients and registered automatically. Prostate contours were drawn on MR-T2 images; seeds were found and matched in successive CT images. Prostate volume and dimensions, seed movements, and prostate dose metrics V200, V150, V100 and D90 were calculated, and their dynamic behaviors quantified in an operationally defined prostate coordinate system., Results: Cohort-averaged reductions in prostate A-P dimension (∼8%) and L-R dimension (∼5%) inferred from seed movements agreed with those obtained from contour measurements, whereas prostate volume and S-I dimension (implant direction) reductions inferred from seed movements were overestimated by about 30%. Average overall seed movement was 4.8 ± 3.0 mm, of which the only identifiable systematic component was resolution of prostate edema. Cohort-averaged ratios of prostate V200, V150, V100, and D90 on day 30 relative to day 0 were 1.67, 1.33, 1.02, and 1.08, respectively., Conclusions: Postimplant prostate size reduction in the SI (implant) direction cannot reliably be inferred from stranded seed movements. Apart from large-scale migration, residual seed movements relative to the prostate after accounting for edema resolution appear to be random. Prostate V100 and D90 changes 30 days post implant are modest, whereas those for V150 and V200 are substantial., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Abstract: To discharge waste liquid containing radioactive iodine into sewage systems, long-term storage or dilution with a large amount of water may be required until the radioactivity concentration reduces below the standard value. Processing the waste liquid could be easier if radioactive iodine could be separated from the water. This study verified the effectiveness of superabsorbent polymer and α-cyclodextrin as treatment agents to separate radioactive iodine from waste liquids. Sodium iodide (Na 125 I) was added to purified water and artificial urine to prepare simulated waste liquids containing iodine equivalent to the urine of patients treated with radioactive iodine. The as-prepared simulated waste liquid was poured into a container with superabsorbent polymer and left for 90 d. The residual iodine rate in the simulated waste liquid was estimated by measuring 125 I radioactivity. When the water was sufficiently dried, residual iodine rates on day 15 were 0.102 and 0.884 in the simulated waste liquids comprising purified water and artificial urine, respectively. The simulated waste liquid comprising purified water with 5% α-cyclodextrin absorbed by 1 g of superabsorbent polymer had a residual rate of 0.980. Moreover, the residual rate of simulated waste liquid comprising artificial urine with 2% α-cyclodextrin absorbed by 1 g of SAP was 0.949. Superabsorbent polymer combined with α-cyclodextrin was an effective treatment agent for separating radioactive iodine from waste liquids., (Copyright © 2024 Health Physics Society.)

Background: Trop-2 is closely related to the development and progression of a variety of tumours and poor prognosis. This study aimed to construct an iodine-124 ( 124 I)-labelled antibody-drug conjugate (ADC) positron emission tomography (PET) probe which could noninvasively image Trop-2 in vivo, providing an important method for the diagnosis of tumours with high Trop-2 expression in clinical practice and monitoring their treatment., Methods: In this study, a novel Trop-2-targeting molecular probe, 124 I-IMMU-132, was constructed to better reveal the expression of Trop-2. The targeting and binding abilities of the probe to Trop-2-positive tumours were investigated in Capan-1/MDA-MB-468/Mcf-7 cells and their animal models., Results: The constructed 124 I-IMMU-132 probe maintained both reliable radiochemical characteristics and binding affinity (K d = 2.200 nmol/L). The uptake of the probe by Trop-2-positive Capan-1/MDA-MB-468 cells increased in a time-dependent manner. The probe bound specifically to Capan-1/MDA-MB-468 tumours in vivo. The SUVmax Tumour/muscle ratio gradually increased with time, from 4.30 ± 0.55-10.78 ± 1.80 (p < 0.01) in the Capan-1 model and from 8.84 ± 0.95-32.20 ± 2.9 (p < 0.001) in the MDA-MB-468 model. The biodistribution and pharmacokinetics of 124 I-IMMU-132 in a mouse model were consistent with the imaging results, and the dosimetry estimation in humans was acceptable., Conclusions: 124 I-IMMU-132 PET is a promising imaging technique for delineating Trop-2-positive tumours. It has great potential in early diagnosis and targeted selection of patients that could benefit from its application., Competing Interests: Declaration of Competing Interest We declare that none of our authors have financial or other conflicts of interest that might be construed as influencing the results or interpretation of our study. This study has not been presented anywhere else., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Exogenous iodine interferes with the uptake of radioactive iodine ( 131 I) by the thyroid gland. This has potential implications for the treatment of cats with hyperthyroidism that have recently undergone computed tomography (CT) with IV administration of iodinated contrast medium (ICM)., Hypothesis: To determine the time to normalize urinary iodine clearance after administration of ICM. We hypothesized that it would require 4 weeks for urinary iodine concentration (UIC) to decrease to baseline after IV administration of ICM., Animals: Ten healthy adult neutered male cats., Methods: All cats were sedated and received Iopamidol at a dose of 2 mL/kg (600 mg/kg). Urinary iodine and creatinine concentrations were measured before administration of Iopamidol and on days 1, 2, 3, 7, 10 and weeks 2 to 6 after administration. The urinary iodine-to-creatinine ratio (UICR) was calculated. Outcome variables were modeled using a linear mixed-effects model., Results: Urinary iodine concentration increased 37- to 884-fold on Day 1 after ICM injection and returned to baseline during Week 2. Compared with baseline, UIC was significantly increased for Days 1 to 7 (all P < .001); UC was significantly lower for Days 1 to 10 (all P < .03); and UICR was significantly increased from Days 1 to 10 (all P < .001, except Day 10 P = .05)., Conclusions: Urinary clearance of iodine after IV administration of ICM requires 10 days to return to baseline in healthy cats. A 2-week interval between the iodinated contrast study and 131 I treatment could be appropriate but needs to be confirmed in hyperthyroid cats., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Claudin18.2 ( CLDN18.2), due to its high expression in various gastric cancer tissues, is considered an optimal target for antitumor drug molecules. In this study, we obtained the labeled compounds of [ 125 I]I-zolbetuximab using the Iodogen method. Under the optimum labeling conditions, the molar activity of [ 125 I]I-zolbetuximab was 1.75 × 10 2 GBq/μmol, and the labeling efficiency was more than 99%. The labeled compounds exhibited excellent in vitro stability in both phosphate buffer saline (PBS, pH = 7.4) and fetal bovine serum systems (FBS) (radiochemical purity >90% at 72 h). The uptake percentage of [ 125 I]I-zolbetuximab in MKN45-CLDN18.2 cells is 24.69 ± 0.84% after 6 h. The saturation binding assay and specificity assay further demonstrated the high specificity of [ 125 I]I-zolbetuximab for CLDN18.2. The long retention at the tumor site and rapid metabolic clearance at other organ sites of [ 125 I]I-zolbetuximab were observed in small-animal SPECT-CT imaging. The same trend was also observed in the biodistribution study. Due to the excellent targeting ability of zolbetuximab for CLDN18.2, [ 125 I]I-zolbetuximab exhibits strong specific binding and retention with cells and tumors highly expressing CLDN18.2. However, the balance between mAb's longer cycle time in vivo and targeting binding and retention ability should be intensively considered for using this kind of radiopharmaceutical in the diagnosis and treatment of CLDN18.2-positive gastric cancer.

The present study aimed to clarify the hypothesis that auger emitter 125 I particles in combination with PARP inhibitor Olaparib could inhibit pancreatic cancer progression by promoting antitumor immune response. Pancreatic cancer cell line (Panc02) and mice subcutaneously inoculated with Panc02 cells were employed for the in vitro and in vivo experiments, respectively, followed by 125 I and Olaparib administrations. The apoptosis and CRT exposure of Panc02 cells were detected using flow cytometry assay. QRT-PCR, immunofluorescence, immunohistochemical analysis, and western blot were employed to examine mRNA and protein expression. Experimental results showed that 125 I combined with Olaparib induced immunogenic cell death and affected antigen presentation in pancreatic cancer. 125 I in combination with Olaparib influenced T cells and dendritic cells by up-regulating CD4, CD8, CD69, Caspase3, CD86, granzyme B, CD80, and type I interferon (IFN)-γ and down-regulating Ki67 in vivo. The combination also activated the cyclic GMP-AMP synthase stimulator of IFN genes (Sting) pathway in Panc02 cells. Moreover, Sting knockdown alleviated the effect of the combination of 125 I and Olaparib on pancreatic cancer progression. In summary, 125 I in combination with Olaparib inhibited pancreatic cancer progression through promoting antitumor immune responses, which may provide a potential treatment for pancreatic cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Radioiodine (I-131) therapy for hyperthyroidism is a well-established and safe treatment option. This study aimed to investigate the relationship between the computed tomography (CT) value and the function and volume of the thyroid gland by identifying the factors that induce changes in the CT value of patients with hyperthyroidism., Methods: This retrospective study evaluated 38 patients with Graves' disease and 10 patients with Plummer disease. To obtain the mean CT value and volume of the thyroid gland, the entire thyroid gland was set as the region of interest. A test dose of 3.7 MBq I-131 was administered before initiating I-131 therapy, and the radioiodine uptake (RIU) rate was assessed after 3, 24, 96, and 168 h. An approximate curve was plotted based on the RIU values obtained, and the effective half-life (EHL) was calculated. The correlation between the mean CT value and the volume of the thyroid gland, 24-h RIU, EHL, and the free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and TSH receptor antibody (TRAb) levels was evaluated., Results: The CT value exhibited a significant positive correlation with EHL in patients with Graves' disease (r = 0.62, p < 0.0001) as well as patients with Plummer disease (r = 0.74, p < 0.05). However, it did not display any correlation with the remaining parameters., Conclusion: The CT value is significantly correlated with EHL, suggesting that it reflects thyroid function and is mainly related to the factors associated with iodine discharge., (© 2024. The Author(s).)

Abstract: Various factors leading to unexpected false-positive 131 I uptake have been extensively studied in patients with differentiated thyroid carcinoma. In this case, we present a patient who underwent achalasia surgery and subsequently exhibited abnormal 131 I uptake on SPECT/CT imaging. The patient was a known case of papillary thyroid carcinoma that suggested to 131 I therapy. 131 I SPECT/CT showed linear increased activity in the distended esophagus., Competing Interests: Conflicts of interest and sources of funding: This research was supported by the National Natural Science Foundation of China (81801737), Foundation of Hubei Province Key Laboratory of Molecular Imaging (2020fzyx016 and 2022fzyx018) and Hubei Provincial Natural Science Foundation Project (2023AFB342)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: For the custom-built construction of eye plaques, the iodine (I-125) seeds of different source strengths are recycled in our eye plaque program. To return I-125 seeds to the correct lot, we developed a novel 3D-printed conical plaque QA holder for relative assay for eye plaques., Materials and Methods: A universal 3D-printed conical plaque holder was designed to accommodate six plaque sizes and fit reproducibly in a well-type dose calibrator. A reproducibility test was used to compare the plaque placement consistency in the holder versus without the holder. Plaque assays were performed for assembled plaques both before implant and after explant. The explant reading was compared with the implant reading adjusted for decay, and the relative error was calculated. The plaque response fraction (PRF) is defined as the fraction of well chamber implant reading over the total seed strength for a plaque. The PRF was aggregated for each individual plaque to confirm the seed lot before implant., Results: The reproducibility test showed the chamber reading's relative standard deviation of 0.40% with the QA holder compared to 0.68% without it. The batch relative assay was performed for 251 plaques. The absolute value of measurement deviation between explant and decay-corrected implant readings is 0.89% ± 0.86% (mean ± standard deviation). The PRFs for individual plaques range from 36.49% to 49.87%, with a maximum standard deviation of 2%., Conclusions: This novel 3D-printed QA holder provides reproducible setup for assaying assembled eye plaques in a well chamber. Batch relative assay can validate the seed batch used and plaque integrity during the implant without assaying individual seeds, saving valuable physicist time and radiation exposure from seed handling., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

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 131 I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). With the presence of 50 µCi mL -1 131 I, 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 131 I-based radiotherapy. The in vivo experiment proves that intratumoral co-adminstration of 131 I (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., (© 2024 Wiley‐VCH GmbH.)

Abstract: A 75-year-old woman with papillary thyroid carcinoma who underwent 131 I radioiodine treatment was incidentally found to have an established left cerebral infarct demonstrating 131 I uptake on posttherapy whole-body scan. False-positive iodine accumulation can occur in benign processes and other malignancies, necessitating awareness among nuclear medicine physicians to avoid misdiagnosing metastatic disease. SPECT/CT can be utilized to enhance diagnostic accuracy when needed., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Multiple high doses of 131 I 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 131 I therapy, explore the interactions, and construct diagnostic models reflecting enteric microecology based on 131 I therapy., Methods: A total of 81 patients were recruited for the first 131 I therapy ( 131 I-1st), among whom 16 received a second course ( 131 I-2nd) after half a year. Fecal samples were collected 1 day before (Pre- 131 I-1st/2nd) and 3 days after (Post- 131 I-1st/2nd) 131 I 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- 131 I-1st and other groups throughout the two courses of 131 I treatment. In the Post- 131 I-1st group, the beneficial bacteria Bifidobacterium, Lachnoclostridium, uncultured&#95;bacterium&#95;f&#95;Lachnospiraceae, and Lachnospiraceae&#95;UCG004 were abundant and the radiation-sensitive pathways of linoleic acid (LA), arachidonic acid, and tryptophan metabolism were inhibited compared with the Pre- 131 I-1st group. Compared with the Pre- 131 I-1st group, the Pre- 131 I-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- 131 I-2nd groups compared with those between the Pre/Post- 131 I-1st groups. A complex co-occurrence was observed between 6 genera and 11 metabolites, with Lachnoclostridium, Lachnospiraceae&#95;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 131 I therapy., Conclusions: Different stages of 131 I therapy exert various effects on gut microecology, which play an essential role in regulating radiotoxicity and predicting the therapeutic response., (© 2024. The Author(s).)

[ 123 I]β-methyl-p-iodophenyl-pentadecanoic acid ([ 123 I]BMIPP), which is used for nuclear medicine imaging of myocardial fatty acid metabolism, accumulates in cancer cells. However, the mechanism of accumulation remains unknown. Therefore, this study aimed to elucidate the accumulation and accumulation mechanism of [ 123 I]BMIPP in cancer cells. We compared the accumulation of [ 123 I]BMIPP in cancer cells with that of [ 18 F]FDG and found that [ 123 I]BMIPP was a much higher accumulation than [ 18 F]FDG. The accumulation of [ 123 I]BMIPP was evaluated in the presence of sulfosuccinimidyl oleate (SSO), a CD36 inhibitor, and lipofermata, a fatty acid transport protein (FATP) inhibitor, under low-temperature conditions and in the presence of etomoxir, a carnitine palmitoyl transferase I (CPT1) inhibitor. The results showed that [ 123 I]BMIPP accumulation was decreased in the presence of SSO and lipofermata in H441, LS180, and DLD-1 cells, suggesting that FATPs and CD36 are involved in [ 123 I]BMIPP uptake in cancer cells. [ 123 I]BMIPP accumulation in all cancer cell lines was significantly decreased at 4 °C compared to that at 37 °C and increased in the presence of etomoxir in all cancer cell lines, suggesting that the accumulation of [ 123 I]BMIPP in cancer cells is metabolically dependent. In a biological distribution study conducted using tumor-bearing mice transplanted with LS180 cells, [ 123 I]BMIPP highly accumulated in not only LS180 cells but also normal tissues and organs (including blood and muscle). The tumor-to-intestine or large intestine ratios of [ 123 I]BMIPP were similar to those of [ 18 F]FDG, and the tumor-to-large-intestine ratios exceeded 1.0 during 30 min after [ 123 I]BMIPP administration in the in vivo study. [ 123 I]BMIPP is taken up by cancer cells via CD36 and FATP and incorporated into mitochondria via CPT1. Therefore, [ 123 I]BMIPP may be useful for imaging cancers with activated fatty acid metabolism, such as colon cancer. However, the development of novel imaging radiotracers based on the chemical structure analog of [ 123 I]BMIPP is needed.

Zolbetuximab (IMAB362), a monoclonal antibody targeting Claudin18.2 (CLDN 18.2), demonstrates a significant clinical benefit in patients with advanced gastroesophageal cancers. The noninvasive assessment of CLDN18.2 expression through molecular imaging offers a potential avenue for expedited monitoring and the stratification of patients into risk groups. This study elucidates that CLDN18.2 is expressed at a noteworthy frequency in primary gastric cancers and their metastases. The iodogen method was employed to label IMAB362 with 123 I/ 131 I. The results demonstrated the efficient and reproducible synthesis of 123 I-IMAB362, with a specific binding affinity to CLDN18.2. Immuno-single-photon emission computed tomography (SPECT) imaging revealed the rapid accumulation of 123 I-IMAB362 in gastric cancer xenografts at 12 h, remaining stable for 3 days in patient-derived tumor xenograft models. Additionally, tracer uptake of 123 I-IMAB362 in MKN45 cells surpassed that in MKN28 cells at each time point, with tumor uptake correlating significantly with CLDN18.2 expression levels. Positron emission tomography/computed tomography imaging indicated that tumor uptake of 18 F-FDG and the functional/viable tumor volume in the 131 I-IMAB362 group were significantly lower than those in the 123 I-IMAB362 group on day 7. In conclusion, 123 I-IMAB362 immuno-SPECT imaging offers an effective method for direct, noninvasive, and whole-body quantitative assessment of tumor CLDN18.2 expression in vivo. This approach holds promise for accelerating the monitoring and stratification of patients with gastric cancer.

Abstract: A 33-year-old woman was referred for radioiodine 6 months after total thyroidectomy and neck dissection for papillary thyroid cancer. Posttherapy whole-body 131 I scintigraphy showed not only the known activity in the neck but also accumulated activity in both feet. SPECT/CT revealed focal uptake in bilateral great toenails. On further clinical evaluation and follow-up, the patient was diagnosed as paronychia of the great toenails., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to develop and psychometrically evaluate a patient-reported outcome measure (PROM), SAlivary, LAcrimal, NaSal (SALANS), to document patients' symptoms after radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC)., Methods: We generated and iteratively revised SALANS items based on expert input, focus group discussions and feedback from cognitive testing (n = 17). We administered an initial SALANS measure with 39 items to patients diagnosed with DTC in the past two years (n = 105). Exploratory factor analysis (EFA) examined the factor structure of the SALANS items. We assessed the consistency reliability and related the total and subscale scores of the final SALANS to existing PROMs to assess validity., Results: The final SALANS consisted of 33 items and six subscales (sialadenitis, taste, xerostomia, dry eyes, epiphora, and nasal) with six factors extracted by EFA. The six subscales demonstrated good internal reliability (α range = 0.87-0.92). The SALANS total score showed good convergent validity with the Xerostomia Inventory (r = 0.86) and good discriminant validity with a measure of spirituality (r =  - 0.05). The mean SALANS total score was significantly higher (d = 0.5, p < 0.04) among patients who had RAI compared to those who did not have RAI., Conclusion: Preliminary evidence suggests that SALANS is a novel and reliable PROM to assess the type and frequency all symptoms experienced after RAI treatment for DTC. Future work is needed to further validate and develop the scale., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Abstract: A 10-year-old hypertensive girl underwent 131 I-MIBG scan to rule out neural crest derived tumor. The whole-body images revealed diffuse intense tracer uptake in the right kidney, which persisted in 96-hour images as well. CT renal angiography revealed 90% to 95% right renal artery stenosis. Thereafter, she underwent baseline and angiotensin receptor blockade renal dynamic imaging, which revealed hemodynamically significant renal artery stenosis. Pattern of diffuse and intense 131 I-MIBG uptake, albeit rare, still warrants further evaluation to rule out renal artery stenosis and investigate its hemodynamic significance for appropriate management., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Patients and Methods: The primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response, blood pressure control, safety, overall and progression-free survival rates, MIBG uptake, and correlations with genetic background., Results: The study included 25 patients. Twenty-four patients had distant metastases, 17 (68%) had hormonally active tumors, and 13 (52%) had previously received antineoplastic treatment. In 24 evaluable patients, the ORR was 38%, including 2 patients with complete response, and the DCR was 83%; median time to response was 12.5 months (95% confidence interval, 4.6-25.1). Twelve patients had sporadic disease, among whom the ORR was 25% and DCR was 83%. Twelve patients had hereditary disease ( SDHB , VHL , RET ); among these, the ORR was 50%, and DCR was 83%. Plasma metanephrines normalized in 30% of patients and improved by greater than 50% in 46%. Sixteen patients had hormonally active tumors and hypertension; in 9 (56%) of these, blood pressure normalized, leading to discontinuation of antihypertensive therapy.The most common adverse events were grades 1-2 nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Reversible grades 3-4 myelosuppression were seen in 7 patients (28%). One patient had fatal pneumonitis., Conclusions: HSA- 131 I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation., Competing Interests: Conflicts of interest and sources of funding: YL has received research support from Lantheus Pharmaceuticals. CJ has received research support from Progenics/Lantheus Pharmaceuticals, Exelixis, and MSD. RAW, VBB, SS, CLP, GX, SGW, JV, and MAH do not have disclosures., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to compare tumor lesion detectability and diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) and radioiodine-labeled meta-iodo-benzylguanidine (mIBG) imaging techniques in patients with metastatic pheochromocytoma and paraganglioma (PPGL). This retrospective study included 13 patients had pheochromocytoma and 5 had paraganglioma, who were all suspected of having metastatic tumors. Each patient underwent WB-MRI and 123 I-mIBG as a pretreatment screening for 131 I-mIBG therapy. Two expert reviewers evaluated WB-MRI, 123 I-mIBG images, and post-therapy 131 I-mIBG images for the presence of metastatic lesions in the lungs, bones, liver, lymph nodes, and other organs. Diagnostic measures for detecting metastatic lesions, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristics (ROC)-area under the curve (AUC), were calculated for each imaging technique. We analyzed WB-MRI images for detecting metastatic lesions, which demonstrated sensitivity, specificity, accuracy, PPV, NPV, and AUC of 82%, 97%, 90%, 96%, 86%, and 0.92, respectively. These values were 83%, 95%, 89%, 94%, 86%, and 0.90 in 123 I-mIBG images and 85%, 92%, 89%, 91%, 87%, and 0.91 in post-therapy 131 I-mIBG images, respectively. Our results reveal the comparable diagnostic accuracy of WB-MRI to one of the mIBG images., (© 2024. The Author(s).)

Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers ( 131 I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

With advances in radioactive particle implantation in clinical practice, Iodine-125 ( 125 I) seed brachytherapy has emerged as a promising treatment for cholangiocarcinoma (CCA), showing good prognosis; however, the underlying molecular mechanism of the therapeutic effect of 125 I seed is unclear. To study the effects of 125 I seed on the proliferation and apoptosis of CCA cells. CCA cell lines, RBE and HCCC-9810, were treated with reactive oxygen species (ROS) scavenger acetylcysteine (NAC) or the p53 functional inhibitor, pifithrin-α hydrobromide (PFTα). Cell counting kit-8 (CCK-8) assay, 5-bromo-2-deoxy-uridine (BrdU) staining, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry assay were performed to test the radiation-sensitivity of 125 I seed toward CCA cells at different radiation doses (0.4 mCi and 0.8 mCi). 2,7-dichlorofluorescein diacetate (DCF-DA) assay, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot analysis were performed to assess the effect of 125 I seed on the ROS/p53 axis. A dose-dependent inhibitory effect of 125 I seeds on the proliferation of CCA cells was observed. The 125 I seed promoted apoptosis of CCA cells and induced the activation of the ROS/p53 pathway in a dose-dependent manner. NAC or PFTα treatment effectively reversed the stimulatory effect of 125 I seed on the proliferation of CCA cells. NAC or PFTα suppressed apoptosis and p53 protein expression induced by the 125 I seed. 125 I seed can inhibit cell growth mainly through the apoptotic pathway. The mechanism may involve the activation of p53 and its downstream apoptotic pathway by up-regulating the level of ROS in cells., (© 2024. The Author(s).)

Abstract: Differentiated thyroid carcinoma constitutes over 90% of all thyroid cancers. The standard treatment approach involves total or near-total thyroidectomy with or without neck dissection followed by 131 I whole-body scintigraphy (WBS) to detect local or distant metastases. Radioiodine offers high sensitivity and specificity for detection of metastatic disease in well differentiated thyroid carcinoma. However, despite its high accuracy, 131 I WBS demonstrates false-positive results, mostly at inflammatory or infective site. These false-positive radioiodine accumulation can lead to misdiagnosis and unwarranted radioiodine treatment. This case presents localization of 131 I to the suture site granuloma leading to false-positive results on 131 I WBS., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The lack of an efficient way to screen patients who are responsive to immunotherapy challenges PD1/CTLA4-targeting cancer treatment. Immunotherapeutic efficacy cannot be clearly determined by peripheral blood analyses, tissue gene markers or CT/MR value. Here, we used a radionuclide and imaging techniques to investigate the novel dual targeted antibody cadonilimab (AK104) in PD1/CTLA4-positive cells in vivo., Methods: First, humanized PD1/CTLA4 mice were purchased from Biocytogen Pharmaceuticals (Beijing) Co., Ltd. to express hPD1/CTLA4 in T-cells. Then, mouse colon cancer MC38-hPD-L1 cell xenografts were established in humanized mice. A bispecific antibody targeting PD1/CTLA4 (AK104) was labeled with radio-nuclide iodine isotopes. Immuno-PET/CT imaging was performed using a bispecific monoclonal antibody (mAb) probe 124 I-AK104, developed in-house, to locate PD1 + /CTLA4 + tumor-infiltrating T cells and monitor their distribution in mice to evaluate the therapeutic effect., Results: The 124 I-AK104 dual-antibody was successfully constructed with ideal radiochemical characteristics, in vitro stability and specificity. The results of immuno-PET showed that 124 I-AK104 revealed strong hPD1/CTLA4-positive responses with high specificity in humanized mice. High uptake of 124 I-AK104 was observed not only at the tumor site but also in the spleen. Compared with PD1- or CTLA4-targeting mAb imaging, 124 I-AK104 imaging had excellent standard uptake values at the tumor site and higher tumor to nontumor (T/NT) ratios., Conclusions: The results demonstrated the potential of translating 124 I-AK104 into a method for screening patients who benefit from immunotherapy and the efficacy, as well as the feasibility, of this method was verified by immuno-PET imaging of humanized mice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aim: ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 ( 131 I) and technetium-99m ( 99m Tc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Results: Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn- lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99m Tc and 131 I showed different biodistribution patterns, with 99m Tc exhibiting higher values in the liver, spleen, and kidneys, while 131 I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn- tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™ 99m Tc. Conclusions: These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery.

Thyroid follicular tumours may take up iodide via the sodium-iodide symporter. Knowledge of iodide uptake could then allow treatment with I-131 in dogs with high-risk tumours. The objective of this study was to determine the relationship between clinically detectable iodide uptake (as determined by scintigraphy and/or thyroxine concentrations) and sodium iodide symporter immunohistochemical labelling on histologically fixed thyroid tumours. Nineteen dogs were identified who were diagnosed with thyroid carcinoma and underwent surgery from November 2017 to July 2021. All had recorded thyroid hormone concentrations and were hyperthyroid and/or underwent preoperative nuclear imaging using planar scintigraphy (technetium-99m or I-123), or I-124 PET-CT. All dogs subsequently underwent surgery to remove the thyroid mass. Twenty-two tumours were submitted for histopathologic analysis immediately following surgery, which confirmed a diagnosis of thyroid carcinoma for each tumour. Images and/or thyroid hormone concentrations were reviewed for the included cases, and tumours were sorted into an avid/functional group (group 1) and a non-avid/functional group (group 2). The tumour tissues were re-examined histologically using sodium iodide symporter (NIS) immunohistochemistry (IHC). Group 1 contained 15 avid/functional tumours. Twelve of these tumours had membranous NIS IHC labelling. Group 2 contained 7 non-avid tumours. One of these tumours had membranous NIS IHC labelling. This resulted in an overall sensitivity and specificity for identification of avid/functional tumours with membranous NIS of 80.0% and 85.7%, respectively. NIS IHC may predict ion trapping in canine follicular thyroid tumours. Further studies using iodide-based imaging are warranted to better determine the clinical utility of this diagnostic modality., (© 2024 John Wiley & Sons Ltd.)