Abstract
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.
Highlights
Prostate cancer is the most common cancer, and one of the leading life-threatening malignancies among men [1]
The radiochemical purity (RCP) of [99m Tc]Tc-CNGU was assessed by thin layer chromatography (TLC) with a high RCP ( 97.3 ± 0.06%)
The TLC results revealed that the RCP of the complex remained at more than 90% after a 6 h incubation either in the reaction mixture at room temperature or in mouse serum at 37 ◦ C, indicating the good in vitro stability of [99m Tc]Tc-CNGU (RCP ≥ 93.5 ± 0.09%)
Summary
Prostate cancer is the most common cancer, and one of the leading life-threatening malignancies among men [1] Both new cases and deaths as a result of prostate cancer have been on the rise in recent years [2]. New radioactive imaging agents bearing a glutamate-urea-based PSMA-targeted. It is necessary to develop available 99m Tc-labeled PSMA inhibitor for the routine clinical imaging of prostate cancer. We were encouraged to prepare a stable 99m Tc-labeled, urea-based, PSMA-targeted ligand containing an isonitrile group and investigate the PSMA-specific imaging of prostate cancer in a mouse model. A novel urea-based PSMA inhibitor containing an isonitrile (CNGU) was synthesized and labeled with 99m Tc to prepare [99m Tc]Tc-CNGU. The potential of [99m Tc]Tc-CNGU for the imaging of prostate cancer was evaluated
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