Design and characterization of a novel prostate-specific membrane antigen-targeted radioligand modified with a fatty acid albumin binder for optimized circulation half-life.

ABSTRACT:

Background

The March 2022 approval of [¹⁷⁷Lu]Lu-PSMA-617-the first targeted radioligand therapy (TRT) for metastatic castration-resistant prostate cancer (mCRPC)-addressed a critical need in therapeutic diagnostics. However, approximately 30% of patients fail to respond to PSMA-targeted therapies, with suboptimal pharmacokinetics implicated as a key factor. To address this challenge, fatty acids, known for their role in binding albumin and enhancing drug pharmacokinetics, were explored. Although commonly used in small molecules and peptides, their application in radiopharmaceuticals remains limited. In response, a novel fatty acid-modified PSMA-targeting agent was developed to optimize pharmacokinetics by enhancing circulation half-life, tumor uptake, radioligand selectivity, and s

SUBMITTER: Zeng S 

PROVIDER: S-EPMC12474822 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature