Synthesis\nand Evaluation of <sup>99m</sup>Tc-Labeled <sub>D</sub>Pro-Gly-Containing\nTracers Targeting PSMA

The specific expression of prostate-specific membrane\nantigen (PSMA)\nmakes it an ideal target for the diagnosis and treatment of prostate\ncancer. Currently, many <sup>99m</sup>Tc-labeled PSMA-targeted tracers\nhave been developed. However, the high renal uptake of these <sup>99m</sup>Tc-labeled tracers is a common problem that limits their\nclinical application. In this work, the ligand (EUKPG) using <sub>D</sub>Pro-Gly as the linker was synthesized and three <sup>99m</sup>Tc-labeled complexes ([<sup>99m</sup>Tc]Tc-EUKPG-EDDA, [<sup>99m</sup>Tc]Tc-EUKPG-TPPTS, [<sup>99m</sup>Tc]Tc-EUKPG-TPPMS) with different\ncoligands were prepared and evaluated. Among them, [<sup>99m</sup>Tc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties,\nwith significantly reduced uptake in the kidney (14.04 ± 0.23%\nID/g), rapid clearance and low uptake in nontarget organs, thus making\nit to exhibit high tumor-to-background ratios (tumor/blood: 7.47,\ntumor/muscle: 12.65). Affinity studies have shown that it has high\nspecificity for PSMA both <i>in vivo</i> and <i>in\nvitro</i>. Therefore, [<sup>99m</sup>Tc]Tc-EUKPG-EDDA has great\npotential as a promising molecular tracer to target PSMA for tumor\nimaging.