Optimizing PSMA-617-based inhibitors through charged linker modifications: Insights into structure-activity relationships.

ABSTRACT: Rationale: The introduction of Pluvicto^® ([¹⁷⁷Lu]Lu-vipivotide tetraxetan; [¹⁷⁷Lu]Lu-PSMA-617) marks a milestone in radioligand therapy (RLT) for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). While dose escalation of [¹⁷⁷Lu]Lu-PSMA-617 and alpha-emitting agents like [²²⁵Ac]Ac-PSMA-617 improves efficacy, it is limited by dose-dependent toxicity in critical organs, including kidneys, bone marrow and salivary glands. Modifications of the linker region in PSMA inhibitors have been proven to highly influence the pharmacokinetic profile. The utilization of charged linker moieties resulted in clinically used PSMA-targeting radiotracers such as [¹⁸F]PSMA-1007. This study explores histidine and/or glut

SUBMITTER: Geis NM 

PROVIDER: S-EPMC12775819 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature