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 99mTc to prepare [99mTc]Tc-CNGU with a high radiochemical purity (RCP). The CNGU ligand showed a high affinity toward PSMA (Ki value is 8.79 nM) in LNCaP cells. The [99mTc]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 [99mTc]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 [99mTc]Tc-CNGU is a promising PSMA-specific tracer for the imaging of prostate cancer.

中文翻译：

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[99mTc]Tc-CNGU 作为 PSMA 靶向放射性示踪剂用于前列腺癌成像的制备和生物学评价

前列腺特异性膜抗原 (PSMA) 是一种成熟的生物靶标，在前列腺癌病变表面过度表达。放射性核素标记的小分子 PSMA 抑制剂已被证明是用于诊断和治疗前列腺癌的有前途的 PSMA 特异性药物。在这项研究中，合成了一种含有异腈 (CNGU) 的谷氨酸尿素基 PSMA 靶向配体，并用 99mTc 标记以制备具有高放射化学纯度 (RCP) 的 [99mTc]Tc-CNGU。CNGU 配体在 LNCaP 细胞中显示出对 PSMA 的高亲和力（Ki 值为 8.79 nM）。[99mTc]Tc-CNGU 在体外表现出良好的稳定性和亲水性（log P = -1.97 ± 0.03）。在生物分布研究中，携带 LNCaP 异种移植物的 BALB/c 裸鼠显示该复合物具有高肿瘤吸收率，为 4.86 ± 1.19% ID/g，降低至 1.74 ± 0。预注射选择性 PSMA 抑制剂 ZJ-43 后为 90% ID/g，表明它是 PSMA 特异性试剂。Micro-SPECT 成像表明 [99mTc]Tc-CNGU 具有肿瘤摄取，并且在用 ZJ-43 封闭后图像中摄​​取减少，进一步证实了其 PSMA 特异性。这项工作中的所有结果表明，[99mTc]Tc-CNGU 是一种很有前途的 PSMA 特异性示踪剂，用于前列腺癌的成像。