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

## TL;DR

This study develops and tests a new PSMA-targeted imaging agent for prostate cancer, showing promising results in preclinical models.

## Contribution

The novel PSMA tracer 68Ga-NOTA-GC-PSMA is introduced with demonstrated high specificity and imaging potential for prostate cancer.

## Key findings

- 68Ga-NOTA-GC-PSMA showed high hydrophilicity and rapid clearance in preclinical models.
- The tracer exhibited high tumor cell uptake and favorable tumor-to-muscle and tumor-to-kidney ratios.
- Radioautography confirmed the tracer's targeting of PSMA in human prostate cancer tissues.

## Abstract

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 68Ga-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 68Ga-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 68Ga-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 68Ga-NOTA-GC-PSMA is promising radionuclide imaging of PCa.