Biodistribution and long-term toxicity of neutron-activated Samarium-153 oxide-loaded polystyrene microspheres in healthy rats

IF 3.6 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2025-04-30 DOI:10.1016/j.nucmedbio.2025.109026

Hun Yee Tan , Yin How Wong , Azahari Kasbollah , Mohammad Nazri Md Shah , Basri Johan Jeet Abdullah , Alan Christopher Perkins , Chai Hong Yeong

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Abstract

Purpose

Selective internal radiation therapy (SIRT) is an effective, minimally invasive treatment for intermediate and advanced-stage liver malignancies, particularly when other curative options are not viable. As an alternative to commercially available Yittrium-90 (⁹⁰Y) resin or glass microspheres, we have developed novel radiopharmaceutical, neutron-activated Samarium-153 oxide-loaded polystyrene ([¹⁵³Sm]Sm₂O₃-PS) microspheres for SIRT. The therapeutic efficacy of the formulation has been assessed in our previous study. This extended study aimed to evaluate the biodistribution and long-term toxicity of [¹⁵³Sm]Sm₂O₃-PS microspheres in a healthy Sprague-Dawley (SD) rat model.

Methods

Biodistribution was assessed in six healthy male SD rats following direct intrahepatic injection of radioactive [¹⁵³Sm]Sm₂O₃-PS microspheres. Static whole-body gamma imaging was performed at 1, 24, and 48 hour post-injection. Radioactivity levels in major organs were measured after euthanasia. For long-term toxicity evaluation, eighteen healthy male SD rats were divided into three groups and tested with: (1) decayed [¹⁵³Sm]Sm₂O₃-PS microspheres; (2) 4 % gelatin solution; and (3) untreated control. Over a 12-month period, body weight, body temperature and liver function biomarkers (ALT, AST, ALP and GGT) were monitored. Histopathological evaluations (HPE) of liver tissues were performed after the rats were sacrificed at the end of the study.

Results

The highest radioactivity (25.15 ± 2.32 % injected dose (ID)/g) was observed at the injected site in the liver at 48 h post-injection, with minimal or undetectable radioactivity in other organs, including spleen, bladder, kidneys, lungs, heart, bone, muscle, and blood. No significant changes (p > 0.05) in body weight and body temperature were observed across groups, and no signs of systemic illness were noted in any of the rats. Liver function biomarkers remained within normal physiological ranges in all groups throughout the study. HPE revealed no lesions or severe inflammation in liver tissues across all groups.

Conclusion

[¹⁵³Sm]Sm₂O₃-PS microspheres demonstrated favourable biodistribution and no evidence of systemic or hepatic toxicity over a 12-month period in healthy rats. These findings support the safety profile of the microspheres and their feasibility for further preclinical and clinical trials.

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中子活化负载钐-153氧化物聚苯乙烯微球在健康大鼠体内的生物分布和长期毒性

选择性内放射治疗（SIRT）是中晚期肝脏恶性肿瘤的一种有效的微创治疗方法，特别是在其他治疗方法不可行的情况下。作为市售的钇-90 （90Y）树脂或玻璃微球的替代品，我们开发了新型放射性药物，中子活化的负载钐-153氧化物聚苯乙烯（[153Sm]Sm2O3-PS）微球用于SIRT。我们之前的研究已经评估了该制剂的治疗效果。本扩展研究旨在评估[153Sm]Sm2O3-PS微球在健康SD大鼠模型中的生物分布和长期毒性。方法观察6只健康雄性SD大鼠肝内直接注射放射性[153Sm]Sm2O3-PS微球后的生物分布。在注射后1、24和48小时进行静态全身伽马成像。在安乐死后测量了主要器官的放射性水平。为了进行长期毒性评价，将18只健康雄性SD大鼠分为3组：(1)用衰变的[153Sm]Sm2O3-PS微球进行试验；(2) 4%明胶溶液；(3)未经处理的对照组。在12个月的时间里，监测体重、体温和肝功能生物标志物（ALT、AST、ALP和GGT）。实验结束后处死大鼠，进行肝组织病理学评价（HPE）。结果48 h注射部位肝脏放射性最高（25.15±2.32%注射剂量(ID)/g），其余脏器（脾、膀胱、肾、肺、心脏、骨、肌肉、血液）放射性最低或未检出。无明显变化(p >；各组大鼠体重和体温差异均为0.05)，未见全身性疾病迹象。在整个研究过程中，所有组的肝功能生物标志物都保持在正常的生理范围内。HPE在所有组中均未发现肝组织病变或严重炎症。结论[153Sm]Sm2O3-PS微球在健康大鼠体内具有良好的生物分布，在12个月的时间内无系统性或肝脏毒性。这些发现支持了微球的安全性及其进一步临床前和临床试验的可行性。

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来源期刊

Nuclear medicine and biology 医学-核医学

CiteScore

6.00

自引率

9.70%

发文量

479

审稿时长

51 days

期刊介绍： Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized. These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field. Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.