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 SUVmax in 27 lesions increased between 1 and 2 h after injection (10.60 vs. 14.11). The SUVmax 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.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019 Feb 22 [Epub]
Teli Liu, Chen Liu, Xiaoxia Xu, Fei Liu, Xiaoyi Guo, Nan Li, Xuejuan Wang, Jianhua Yang, Xing Yang, Hua Zhu, Zhi Yang
Key Laboratory of Carcinogenesis and Translational Research (Beijing Ministry of Education), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China; and., Key Laboratory of Carcinogenesis and Translational Research (Beijing Ministry of Education), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China; and ., Department of Nuclear Medicine, Peking University First Hospital, Beijing, China .