전립선암 테라노스틱스 분야에서 PSMA-617의 구조적 통찰 및 새로운 전략

초록

Prostate cancer is the most commonly diagnosed malignancy, and its progression to metastaticcastration-resistant prostate cancer (mCRPC) remains difficult to manage with conventional biomarkers andanatomical imaging alone. Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy has emergedas a promising precision medicine strategy for the treatment of mCRPC. Among currently available PSMA ligands,PSMA-617 has emerged as the leading theranostic platform owing to its rational molecular design, which integratesa Glu-urea-Lys pharmacophore, an optimized linker, and a DOTA chelator to achieve high receptor affinity,favorable pharmacokinetic properties, and compatibility with both diagnostic and therapeutic radionuclides. Thisreview examines the structural characteristics of PSMA-617 and discusses their impact on radiolabeling efficiency,biodistribution, receptor-mediated tumor uptake and retention, and therapeutic efficacy. It also highlights recentadvances in PSMA-targeted radiopharmaceuticals labeled with diagnostic radionuclides, including 68Ga and Al18F,as well as therapeutic radionuclides such as 177Lu and 225Ac. Furthermore, we discuss the preclinical and clinicalevidence supporting the efficacy and safety of 177Lu-PSMA-617 and summarize the recent clinical development ofother PSMA-targeted radiopharmaceuticals. Finally, emerging strategies, including α-particle therapy, albuminbindingligands, and combination therapies, are discussed as promising approaches to enhance therapeutic efficacywhile minimizing off-target toxicity. Overall, this review provides a comprehensive overview of the molecular design,radiopharmaceutical development, preclinical and clinical translation, and future perspectives of PSMA-617-basedtheranostics for precision medicine in prostate cancer.

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