Preparation and Biological Evaluation of [99mTc]Tc-CNGU as a PSMA-Targeted Radiotracer for the Imaging of Prostate Cancer

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 23; p. 5548
• Main Authors: Xiao, Di, Duan, Xiaojiang, Gan, Qianqian, Zhang, Xuran, Zhang, Junbo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.11.2020; MDPI
• Subjects: 99mTc; Animals; Antigens, Surface - metabolism; Chromatography; Glutamate Carboxypeptidase II - metabolism; Humans; isonitrile; Kidneys; Ligands; Male; Mice; Molecular Imaging - methods; Molecular Structure; Nitriles - chemistry; NMR; Nuclear magnetic resonance; Organotechnetium Compounds - chemistry; Prostate cancer; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; PSMA; Radioactive Tracers; Radiopharmaceuticals; SPECT imaging; Technetium - chemistry; Tomography, Emission-Computed, Single-Photon - methods; 99mTc; PSMA; prostate cancer; SPECT imaging; isonitrile
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25235548

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.