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

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.

Preparation and Preliminary Evaluation of a Promising 99mTc-Labeled Isonitrile-Containing 6-Thia-Fatty Acid Derivative for Myocardial Metabolism Imaging

“…After that, the cuprous complexes of isonitriles 15 or 16 were formed by the ligand exchange of isonitriles 12 or 13 with tetrakis(acetonitrile)copper(I) tetrafluoroborate 14 , respectively . The intermediates 15 or 16 were respectively converted to the precursors 17 or 18 through basic hydrolysis of methyl esters and the subsequent acidification …”

“…35 The intermediates 15 or 16 were respectively converted to the precursors 17 or 18 through basic hydrolysis of methyl esters and the subsequent acidification. 36 Additional detailed results and discussion are provided in the Additional Results and Discussion�1. Organic Synthesis of Precursors section on Page S14 of the Supporting Information.…”

Preparation, Biological Evaluation, and First-in-Human Single-Photon Emission Computed Tomography (SPECT) Study of 99mTc-Labeled Prostate-Specific Membrane Antigen (PSMA)-Targeted Radiotracers Containing Triazole with Reduced Kidneys Accumulation

“…In our previously reported study, the kit containing [ 99m Tc]Tc-CNGU, a 99m Tc-labled PSMA radiotracer, was unstable and not preserved at 2−8 °C. 36 Compared with the isocyanidecontaining ligand CNGU, the HYNIC-containing ligand T had better stability, and the quality inspection kit for T-M2 was stable for more than 6 months at 2−8 °C or for one year at −18 °C, which is beneficial for practical storage and dispersal worldwide.…”

A Preclinical Study of an 125I-Labeled PSMA Ligand for Prostate-Cancer Puncture

“…A blocking experiment was performed by treating 22Rv1 and PC3 cells with ZJ43 [ 28 , 29 ] for 15 min, followed by the same steps as for the cell uptake experiment.…”