Optimization of PSMA-I&T radiolabeling with 177Lu

Abstract

Prostate cancer (PCa) is the second most common type of cancer in men and the fifth leading cause of cancer-related mortality worldwide. Metastatic prostate cancer is associated with poor prognosis and reduced life expectancy. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein anchored in the membrane of prostate epithelial cells. It is overexpressed in prostate cancer, particularly in patients with metastatic castration-resistant prostate cancer (mCRPC), and its expression level is widely recognized as being correlated with disease aggressiveness. ^177Lu-PSMA-I&T has emerged as a promising radiopharmaceutical for the treatment of prostate cancer, owing to its specific binding to PSMA through the Glu-urea-Lys pharmacophoric group. The present study aimed to determine the most favorable conditions for labeling PSMA I&T with carrier-added lutetium-177, evaluating the influence of molar ratio, pH, temperature, and reaction time to obtain a radiopharmaceutical with high radiochemical purity (%RP ≥ 95%) without the need for a final purification step. Radiochemical purity was assessed by High-Performance Liquid Chromatography (HPLC) and Thin-Layer Chromatography on silica gel 60 plates (TLC-SG). The results made it possible to define and standardize the optimal conditions for radiolabeling PSMA I&T with carrier-added ^177Lu.