Nuclear medicine and biology · 2025
Biodistribution and long-term toxicity of neutron-activated Samarium-153 oxide-loaded polystyrene microspheres in healthy rats.
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Tan Hun Yee, Wong Yin How, Kasbollah Azahari, Shah Mohammad Nazri Md, Abdullah Basri Johan Jeet, Perkins Alan Christopher, Yeong Chai Hong
Аннотация
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.
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.