Preclinical Evaluation of a Novel PSMA-Targeted Agent (68)Ga-NOTA-GC-PSMA for Prostate Cancer Imaging.

Objectives: Prostate-specific membrane antigen (PSMA)-targeted radioligands are promising diagnostic tools for the targeted positron emission tomography (PET) imaging of prostate cancer (PCa). In present work, we aimed to develop a novel PSMA tracer to provide an additional option for prostate cancer diagnosis. Methods: Our team designed a new structure of the PSMA tracer and evaluated it with cellular experiments in vitro to preliminarily verify the targeting and specificity of (68)Ga-NOTA-GC-PSMA. PET/CT imaging of PSMA-positive xenograft-bearing models in vivo to further validate the in vivo specificity and targeting of the radiotracer. Pathological tissue sections from prostate cancer patients were compared with pathological immunohistochemistry and pathological tissue staining results by radioautography experiments to assess the targeting-PSMA of (68)Ga-NOTA-GC-PSMA on human prostate cancer pathological tissues. Results: The novel tracer showed high hydrophilicity and rapid clearance rate. Specific cell binding and micro-PET imaging experiments showed that (68)Ga-NOTA-GC-PSMA displayed a high specific LNCaP tumor cell uptake (1.70% ± 0.13% at 120 min) and tumor-to-muscle (T/M) and tumor-to-kidney (T/K) ratio (13.87 ± 11.20 and 0.20 ± 0.08 at 60 min, respectively). Conclusions: The novel tracer (68)Ga-NOTA-GC-PSMA is promising radionuclide imaging of PCa.