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Can current preclinical strategies for radiopharmaceutical development meet the needs of targeted alpha therapy?
European Journal of Nuclear Medicine and Molecular Imaging ( IF 9.1 ) Pub Date : 2024-04-27 , DOI: 10.1007/s00259-024-06719-5
Janke Kleynhans , Thomas Ebenhan , Frederik Cleeren , Mike Machaba Sathekge

Preclinical studies are essential for effectively evaluating TAT radiopharmaceuticals. Given the current suboptimal supply chain of these radionuclides, animal studies must be refined to produce the most translatable TAT agents with the greatest clinical potential. Vector design is pivotal, emphasizing harmonious physical and biological characteristics among the vector, target, and radionuclide. The scarcity of alpha-emitting radionuclides remains a significant consideration. Actinium-225 and lead-212 appear as the most readily available radionuclides at this stage. Available animal models for researchers encompass xenografts, allografts, and PDX (patient-derived xenograft) models. Emerging strategies for imaging alpha-emitters are also briefly explored. Ultimately, preclinical research must address two critical aspects: (1) offering valuable insights into balancing safety and efficacy, and (2) providing guidance on the optimal dosing of the TAT agent.



中文翻译:

目前的放射性药物开发临床前策略能否满足靶向α疗法的需求?

临床前研究对于有效评估 TAT 放射性药物至关重要。鉴于目前这些放射性核素的供应链欠佳,必须完善动物研究,以生产最具可转化性且具有最大临床潜力的 TAT 制剂。载体设计至关重要,强调载体、靶标和放射性核素之间协调的物理和生物学特性。 α发射放射性核素的稀缺仍然是一个重要的考虑因素。 Actinium-225 和 Lead-212 似乎是现阶段最容易获得的放射性核素。研究人员可用的动物模型包括异种移植、同种异体移植和 PDX(患者来源的异种移植)模型。还简要探讨了α发射体成像的新兴策略。最终,临床前研究必须解决两个关键方面:(1) 为平衡安全性和有效性提供有价值的见解,(2) 为 TAT 药物的最佳剂量提供指导。

更新日期:2024-04-27
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