Zhang Siqi, Wang Xingkai, Gao Xin, Chen Xueyao, Li Linger, Li Guoqing, Liu Can, Miao Yuan, Wang Rui, Hu Kuan
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, China.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, Lanzhou University, 2019RU066, 730000, Lanzhou, China.
Signal Transduct Target Ther. 2025 Jan 3;10(1):1. doi: 10.1038/s41392-024-02041-6.
Radiopharmaceuticals involve the local delivery of radionuclides to targeted lesions for the diagnosis and treatment of multiple diseases. Radiopharmaceutical therapy, which directly causes systematic and irreparable damage to targeted cells, has attracted increasing attention in the treatment of refractory diseases that are not sensitive to current therapies. As the Food and Drug Administration (FDA) approvals of [Lu]Lu-DOTA-TATE, [Lu]Lu-PSMA-617 and their complementary diagnostic agents, namely, [Ga]Ga-DOTA-TATE and [Ga]Ga-PSMA-11, targeted radiopharmaceutical-based theranostics (radiotheranostics) are being increasingly implemented in clinical practice in oncology, which lead to a new era of radiopharmaceuticals. The new generation of radiopharmaceuticals utilizes a targeting vector to achieve the accurate delivery of radionuclides to lesions and avoid off-target deposition, making it possible to improve the efficiency and biosafety of tumour diagnosis and therapy. Numerous studies have focused on developing novel radiopharmaceuticals targeting a broader range of disease targets, demonstrating remarkable in vivo performance. These include high tumor uptake, prolonged retention time, and favorable pharmacokinetic properties that align with clinical standards. While radiotheranostics have been widely applied in tumor diagnosis and therapy, their applications are now expanding to neurodegenerative diseases, cardiovascular diseases, and inflammation. Furthermore, radiotheranostic-empowered precision medicine is revolutionizing the cancer treatment paradigm. Diagnostic radiopharmaceuticals play a pivotal role in patient stratification and treatment planning, leading to improved therapeutic outcomes in targeted radionuclide therapy. This review offers a comprehensive overview of the evolution of radiopharmaceuticals, including both FDA-approved and clinically investigated agents, and explores the mechanisms of cell death induced by radiopharmaceuticals. It emphasizes the significance and future prospects of theranostic-based radiopharmaceuticals in advancing precision medicine.
放射性药物涉及将放射性核素局部递送至靶向病灶，用于多种疾病的诊断和治疗。放射性药物疗法可直接对靶向细胞造成系统性且不可修复的损伤，在治疗对当前疗法不敏感的难治性疾病方面日益受到关注。随着美国食品药品监督管理局（FDA）批准[镥]镥-多胺基多羧基络合剂-奥曲肽（[Lu]Lu-DOTA-TATE）、[镥]镥-前列腺特异性膜抗原-617（[Lu]Lu-PSMA-617）及其配套诊断剂，即[镓]镓-多胺基多羧基络合剂-奥曲肽（[Ga]Ga-DOTA-TATE）和[镓]镓-前列腺特异性膜抗原-11（[Ga]Ga-PSMA-11），基于靶向放射性药物的治疗诊断学（放射治疗诊断学）在肿瘤学临床实践中越来越多地得到应用，从而开启了放射性药物的新时代。新一代放射性药物利用靶向载体实现放射性核素向病灶的精准递送，避免非靶向沉积，使得提高肿瘤诊断和治疗的效率及生物安全性成为可能。众多研究致力于开发针对更广泛疾病靶点的新型放射性药物，在体内表现出显著性能。这些性能包括高肿瘤摄取、延长的滞留时间以及符合临床标准的良好药代动力学特性。虽然放射治疗诊断学已广泛应用于肿瘤诊断和治疗，但其应用目前正在扩展到神经退行性疾病、心血管疾病和炎症。此外，放射治疗诊断学助力的精准医学正在彻底改变癌症治疗模式。诊断性放射性药物在患者分层和治疗规划中发挥关键作用，从而在靶向放射性核素治疗中改善治疗效果。本综述全面概述了放射性药物的发展历程，包括FDA批准的药物和临床研究药物，并探讨了放射性药物诱导细胞死亡的机制。它强调了基于治疗诊断学的放射性药物在推进精准医学方面的重要性和未来前景。
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