STUDY OF A RADIOPHARMACEUTICAL PRECURSOR TARGETING PROSTATE-SPECIFIC MEMBRANE ANTIGEN

Abstract

Prostate cancer is one of the most commonly diagnosed cancers worldwide. Targeted therapy is an anticancer strategy using short peptides targeting prostate-specific membrane antigen (PSMA). However, short peptides have a number of disadvantages, including low stability in vivo. This problem can be solved by using toxins with an inhibitory cystine knot with a short built in peptide. The aim of the study is to examine the stability and ability of the PSMA/C1-C2 peptide, created on the base of knottin U5-scytotoxin-Sth1a and a short peptide tropic to PSMA, to bind to receptors on the surface of prostate cancer cells and to compare the results with a market image drug PSMA I&T and a specific PSMA inhibitor. Materials and Methods. A solid-phase peptide synthesizer was used for peptide synthesis, chromatography and mass spectrometry were applied for analysis and purification. A competitive inhibition analysis was performed with radiolabeled commercial PSMA I&T in excess of PSMA/C1-C2 and FAM-labeled PSMA/C1-C2 with a specific PSMA inhibitor 2-PMPA. PSMA-positive culture 22Rv1 and PSMA-negative culture PC-3 were used as cell cultures. Chromatography was used to access peptide stability. Results. As a result, it was observed that the synthesized PSMA/C1-C2 structure, created on the basis of knottin and a short peptide, prevents binding of PSMA I&T to receptors on the surface of 22Rv1 cells. The decrease in PSMA/C1-C2 binding in the presence of 2-PMPA suggests that PSMA/C1-C2 is targeted for prostate-specific membrane antigen. In addition, PSMA/C1-C2 peptide has increased stability compared to PSMA I&T.