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

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 <i>in vitro</i> and <i>in vivo</i>. 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.