Optimized production, quality control, biological evaluation and PET/CT imaging of 68Ga-PSMA-617 in breast adenocarcinoma model

Abstract

Abstract Optimized production, quality control and preclinical evaluation of 68Ga-PSMA-617 as a PET radiotracer for PSMA-positive malignancies as well as successful application in imaging of breast adenocarcinomas are reported. 68Ga-PSMA-617 radiolabeling and QC optimization, stability, log P, biodistribution in breast adenocarcinomas-bearing mice (direct and blockade studies) and also PET/CT imaging was performed. 68Ga-PSMA-617 complex was prepared in high radiochemical purity (>96%, ITLC, HPLC) and specific activity of 300–310 GBq/mM at 95 °C using 2–4 micrograms of the peptide in 10 min followed by solid phase purification. The tracer was stable in serum and final formulation for at least 120 min. The log P was −1.98. Western blot test on the tumor cell homogenates demonstrated distinct existence of the PSMA on the surface. The biodistribution of the tracer demonstrated specific kidney and tumor significant uptake using blocking study. Significant tumor:blood and tumor:muscle ratio uptake observed at 30 min post-injection (2.69 and 19.1, respectively). A reduction of 40–80% off tumor uptake in the study time period observed using blocking test. 68Ga-PSMA-617 can be proposing a possible tracer for PET imaging of breast adenocarcinomas and other breast malignancies.