Synthesis and Evaluation of 99mTc-Labeled l-Aspartic Acid as a EuK Polymer Linker for Targeting PSMA to a Novel SPECT Tumor Tracer

Abstract

The development of novel tracers targeting prostate-specific membrane antigen (PSMA) has great potential for improving the diagnosis and treatment of prostate cancer (PCa). This study aimed to improve the absolute tumor uptake and tumor-to-background ratios (TBRs) of this novel PSMA tracer by increasing the number of pharmacophores, Glu-urea-Lys (EuK), that specifically bind to PSMA. We successfully synthesized four radioligands and prepared a total of 12 stable radiotracers by coordinating ^99mTc with various coligands. [^99mTc]Tc-EUKD-EDDA showed the best pharmacokinetic properties both in vitro and in vivo. It effectively increased the absolute uptake in tumors and resulted in good tumor retention. Rapid clearance in nontarget organs resulted in high TBRs. High-contrast SPECT/CT images were obtained within 2–6 h after injection, suggesting that [^99mTc]Tc-EUKD-EDDA has great application potential in time-lapse imaging of PCa, which is important for improving the diagnostic accuracy of PCa in clinical practice.