Radioligands that target prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) have emerged as promising tools for both imaging and therapeutic strategies in prostate cancer. Yet, heterogeneous expression of these receptors in tumors and metastatic lesions can limit the effectiveness of single-target approaches. To address this limitation, dual-targeting radioligands capable of simultaneously binding PSMA and GRPR have been developed. In this study, we report the preclinical evaluation of [68Ga]Ga-BQ7812, a PSMA/GRPR heterodimer designed for PET-based diagnostic imaging of prostate cancer, with the goal of supporting its clinical translation. In vitro assays using PSMA/GRPR-positive PC3-pip cells demonstrated rapid and selective binding to both targets. Biodistribution studies in PC3-pip xenograft-bearing mice revealed highest uptake at 1 hour post-injection in tumor tissue (PSMA+/GRPR+, 10.4 ± 1.0% IA/g), kidneys (PSMA+, 45 ± 16% IA/g), and pancreas (GRPR+, 5.6 ± 0.7% IA/g). By 3 hours post-injection, tumor-to-background ratios improved, reflecting preferential retention of the radioligand in tumor tissue. Additionally, [68Ga]Ga-BQ7812 exhibited low toxicity and an acceptable estimated dosimetry (effective dose = 0.0083 mSv/MBq), supporting its potential for first-in-human studies and further clinical development.
