In Vitro and in Vivo Comparative Study of a Novel 68 Ga-Labeled PSMA-Targeted Inhibitor and 68 Ga -PSMA-11

Abstract

68Ga-radiolabeled small molecules that specifically target prostate specific membrane antigen (PSMA) has been extensively investigated, and some of those tracers have been used in diagnosis of prostate cancer with 68Ga-positron emission tomography (68Ga-PET). Nevertheless, current 68Ga-labeled radiotracers show fair detection rates to metastasized prostate cancer lesions, especially to those with lower level of prostate specific antigen (PSA), which often occur in biochemical recurrence of prostate cancer. The goal of this study was to design and synthesize a new PSMA-targeted radiotracer 68Ga-SC691 with high affinity to prostate cancer cells and excellent pharmacokinetics. To this end, structural optimum was made on the bifunctional group, target motif, and linker while high affinity targeting scaffold was remained. In order to explore its potential in clinical, a comparative study was further performed in vitro and in vivo between 68Ga-SC691 and 68Ga-PSMA-11, the clinically approved tracer for PSMA-positive prostate cancer. SC691 was radiolabeled to provide 68Ga-SC691 in 99% radiolabeling yield under mild conditions. High uptake and internalization ratio into LNCaP cells were observed in in vitro studies. In vivo studies showed that 68Ga-SC691 had a favorable biodistribution property and can specifically accumulate on PSMA-positive LNCaP xenografts visualized by micro-PET/CT. This radiotracer showed excellent PET imaging quality and comparable uptake at LNCaP xenografts if not higher than 68Ga-PSMA-11.