Preparation And Biological Evaluation Of [Tc-99m]Tc-Cngu As A Psma-Targeted Radiotracer For The Imaging Of Prostate Cancer

Prostate-specific membrane antigen (PSMA) is a well-established biological target that is overexpressed on the surface of prostate cancer lesions. Radionuclide-labeled small-molecule PSMA inhibitors have been shown to be promising PSMA-specific agents for the diagnosis and therapy of prostate cancer. In this study, a glutamate-urea-based PSMA-targeted ligand containing an isonitrile (CNGU) was synthesized and labeled with Tc-99m to prepare [Tc-99m]Tc-CNGU with a high radiochemical purity (RCP). The CNGU ligand showed a high affinity toward PSMA (K-i value is 8.79 nM) in LNCaP cells. The [Tc-99m]Tc-CNGU exhibited a good stability in vitro and hydrophilicity (log P = -1.97 +/- 0.03). In biodistribution studies, BALB/c nude mice bearing LNCaP xenografts showed that the complex had a high tumor uptake with 4.86 +/- 1.19% ID/g, which decreased to 1.74 +/- 0.90% ID/g after a pre-injection of the selective PSMA inhibitor ZJ-43, suggesting that it was a PSMA-specific agent. Micro-SPECT imaging demonstrated that the [Tc-99m]Tc-CNGU had a tumor uptake and that the uptake was reduced in the image after blocking with ZJ-43, further confirming its PSMA specificity. All of the results in this work indicated that [Tc-99m]Tc-CNGU is a promising PSMA-specific tracer for the imaging of prostate cancer.