Synthesis and Evaluation\nof <sup>99m</sup>Tc-Labeled l‑Aspartic Acid as a EuK\nPolymer Linker for Targeting\nPSMA to a Novel SPECT Tumor Tracer

The\ndevelopment of novel tracers targeting prostate-specific membrane\nantigen (PSMA) has great potential for improving the diagnosis and\ntreatment of prostate cancer (PCa). This study aimed to improve the\nabsolute tumor uptake and tumor-to-background ratios (TBRs) of this\nnovel PSMA tracer by increasing the number of pharmacophores, Glu-urea-Lys\n(EuK), that specifically bind to PSMA. We successfully synthesized\nfour radioligands and prepared a total of 12 stable radiotracers by\ncoordinating <sup>99m</sup>Tc with various coligands. [<sup>99m</sup>Tc]Tc-EUKD-EDDA showed the best pharmacokinetic properties both <i>in vitro</i> and <i>in vivo</i>. It effectively increased\nthe absolute uptake in tumors and resulted in good tumor retention.\nRapid clearance in nontarget organs resulted in high TBRs. High-contrast\nSPECT/CT images were obtained within 2–6 h after injection,\nsuggesting that [<sup>99m</sup>Tc]Tc-EUKD-EDDA has great application\npotential in time-lapse imaging of PCa, which is important for improving\nthe diagnostic accuracy of PCa in clinical practice.