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

Preclinical studies demonstrate that [¹⁷⁷Lu]Lu-BT-117016, a novel fatty acid-modified PSMA-targeting agent, optimizes albumin binding and harmonizes ligand-isotope half-lives. This results in advantageous biodistribution-characterized by high tumor uptake, rapid non-target clearance, and extended circulation-leading to complete tumor remission in LNCaP models with reduced toxicity. Crucially, [¹⁷⁷Lu]Lu-BT-117016 achieved equivalent efficacy to [¹⁷⁷Lu]Lu-PSMA-617 at 3-6 times lower doses. These findings indicate [¹⁷⁷Lu]Lu-BT-117016's potential as a safer, more potent CRPC therapy enabling reduced dosages and less frequent administration. Further clinical trials are warranted to confirm these benefits.