RT Journal Article SR Electronic T1 Development of a novel PSMA targeted probe labeled witAl18F for prostate cancer imaging: Preclinicaland in-man evaluation JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 58 OP 58 VO 59 IS supplement 1 A1 Teli Liu A1 Chen Liu A1 Hua Zhu A1 Zhi Yang YR 2018 UL http://jnm.snmjournals.org/content/59/supplement_1/58.abstract AB 58Purpose: Prostate cancer (PCa) is common among men in western countries. PSMA (prostate specific membrane antigen), over-expressed in prostate cancer cells, is a promising target for the diagnosis and therapy of PCa. PET/CT imaging with PSMA targeted tracers can noninvasively detect PCa with high specificity. Considering 18F has higher resolution, longer half-life and higher yield, Al18F labeling is more convenient than classic 18F labeling, we developed a PSMA targeted probe labeled with Al18F. Preclinical study was performed to evaluate its potential for clinical application and in-man study was performed to evaluate its detectability for PSMA expressed prostate cancer. Methods: The precursor, NOTA-PSMA, was designed, synthesized and labeled with Al18F to obtain Al18F-PSMA. The in vitro (stability, partition coefficient, cell uptake and binding affinity) and in vivo (stability, pharmacokinetic in blood, single-dose toxicity, Rbiodistribution and micro-PET imaging) experiments were performed to evaluate the possibility of Al18F-PSMA for clinical use. After the evaluation in mice, in-man PET/CT imaging was conducted to evaluate the potential of Al18F-PSMA for clinical diagnosis of PCa and the potential of transformation to clinic. Results Al18F-PSMA was prepared in high radiochemical yield (20-41%) with high radiochemical purity (> 99%) and specific activity (8.8-16.7 GBq/μmol) in 30 min. Al18F-PSMA was hydrophilic, stable and safe under the dose of 1.48 GBq/kg in mice. Al18F-PSMA showed higher uptake in PSMA (+) 22Rv1 cells than in PSMA (-) PC-3 cells (1.32 vs 0.61 IA%/106 cells at 1 h, p< 0.05). The uptake in 22Rv1 tumor (7.87 ±2.37 ID%/g) was higher than that in PC-3 tumor (0.54 ±0.22 ID%/g) and most non-target tissues excepting kidney (14.15±2.32 ID%/g) at 1 h p.i.. Coincident with the result biodistribution, Al18F-PSMA showed higher uptake in 22Rv1 tumor than PC-3 tumor, the uptake in 22Rv1 tumor and kidney could be blocked by excess ZJ-43, a PSMA inhibitor. When compared with most of PSMA targeted probes, Al18F-PSMA showed comparable uptake in PSMA (+) tumor and extremely lower uptake in kidney (14.15±2.32, 113.4±24.4 and 139.4±21.4 ID%/g for Al18F-PSMA, 68Ga-PSMA-617 and 68Ga-PSMA-11 at 1 h p.i., respectively). As reported PSMA targeted probes, Al18F-PSMA PET/CT imaging (1.85-3.7 MBq/kg) on a healthy volunteer showed obviously uptake in PSMA expressing organs at 1 h p.i., and no hematological or biochemical effects was observed. Imaging on a 67-year-old patient (PSA 76.3 ng/mL), abnormal uptake in prostate gland (SUVmax 28.27), lymph nodes (diameter 13 mm, SUVmax 22.72) and bone (SUVmax 35.50) were observed and verified as tumor with Gleason score of 4+4. Conclusion Qualified Al18F-PSMA was prepared and evaluated by in vitro and in vivo experiments. Preclinical and in-man studies showed Al18F-PSMA was PSMA specific with high affinity and with good detectability for PSMA expressing tumors. Further efforts are needed to promote it to clinic. Keywords Al18F PSMA, PET imaging, prostate cancer