Synthesis and Evaluation of 99mTc-Labeled DPro-Gly-Containing Tracers Targeting PSMA.

Abstract

The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many 99mTc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these 99mTc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using DPro-Gly as the linker was synthesized and three 99mTc-labeled complexes ([99mTc]Tc-EUKPG-EDDA, [99mTc]Tc-EUKPG-TPPTS, [99mTc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [99mTc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both in vivo and in vitro. Therefore, [99mTc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.