Preclinical Evaluation and Pilot Clinical Study of Al18F-PSMA-BCH for Prostate Cancer PET Imaging

Prostate-specific membrane antigen (PSMA)-targeted radioligands have played an important role in the diagnosis of prostate cancer. In this study, we developed an Al¹⁸F-labeled radiotracer and evaluated its potential for prostate cancer imaging. Methods: Al¹⁸F-PSMA-BCH (BCH is Beijing Cancer Hospital) was efficiently prepared manually. The binding affinity to PSMA was evaluated in vitro using the 22Rv1 (PSMA-positive) cell line. Small-animal PET imaging, biodistribution studies of Al¹⁸F-PSMA-BCH in mice bearing 22Rv1 and PC-3 (PSMA-negative) xenografted tumors, and a comparison with ⁶⁸Ga-PSMA-617 in mice bearing LNCaP tumors were performed. PET/CT imaging was performed on 11 newly diagnosed prostate cancer patients at 1 and 2 h after injection. Biodistribution and preliminary efficacy were evaluated, and radiation dosimetry was estimated using OLINDA/EXM 2.0 software. Results: Al¹⁸F-PSMA-BCH was prepared within 30 min and was found to bind to PSMA with a dissociation constant of 2.90 ± 0.83 nM. Small-animal PET imaging of Al¹⁸F-PSMA-BCH could clearly differentiate 22Rv1 tumors from PC-3 tumors, as confirmed by ex vivo biodistribution data (7.87% ± 2.37% and 0.54% ± 0.22% injected dose/g at 1 h in 22Rv1 and PC-3 tumors, respectively). The uptake of Al¹⁸F-PSMA-BCH in 22Rv1 tumors could be substantially blocked by excess ZJ-43, a PSMA inhibitor. High-level accumulation of Al¹⁸F-PSMA-BCH was observed in PSMA-expressing organs, with increased uptake at later time points. Thirty-seven tumor lesions were detected in 11 patients, and the SUV_max in 27 lesions increased between 1 and 2 h after injection (10.60 vs. 14.11). The SUV_max in primary lesions in patients with high-risk prostate cancer was higher than that in patients with intermediate-risk prostate cancer. The kidneys received the highest estimated dose, 0.135 mGy/MBq, and the effective dose was 0.016 mGy/MBq. Conclusion: Al¹⁸F-PSMA-BCH was conveniently prepared with a reasonable yield within 30 min and showed a promising imaging capability for prostate cancer with reasonable radiation exposure. Al¹⁸F-PSMA-BCH can be used for prostate cancer imaging as a novel ¹⁸F PET radiotracer.