An Albumin-Binding PSMA Ligand with Higher Tumor Accumulation for PET Imaging of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is an ideal target for the diagnosis and treatment of prostate cancer. Due to the short half-life in blood, small molecules/peptides are rapidly cleared by the circulatory system. Prolonging the half-life of PSMA probes has been considered as an effective strategy to improve the tumor detection. Herein, we reported a Cu-labeled PSMA tracer conjugating with maleimidopropionic acid (MPA), Cu-PSMA-CM, which showed an excellent ability to detect PSMA-overexpressing tumors in delayed time. Cell experiments in PSMA-positive 22Rv1 cells, human serum albumin binding affinity, and micro-PET imaging studies in 22Rv1 model were performed to investigate the albumin binding capacity and PSMA specificity. Comparisons with Cu-PSMA-BCH were performed to explore the influence of MPA on the biological properties. Cu-PSMA-CM could be quickly prepared within 30 min. The uptake of Cu-PSMA-CM in 22Rv1 cells increased over time and it could bind to HSA with a high protein binding ratio (67.8 ± 1.5%). When compared to Cu-PSMA-BCH, Cu-PSMA-CM demonstrated higher and prolonged accumulation in 22Rv1 tumors, contributing to high tumor-to-organ ratios. These results showed that Cu-PSMA-CM was PSMA specific with a higher tumor uptake, which demonstrated that MPA is an optional strategy for improving the radioactivity concentration in PSMA-expressing tumors and for developing the ligands for PSMA radioligand therapy.