Synthesis of 68Ga-PSMA-11 and evaluation of its biodistribution and kinetics in mice

Abstract

Objective To synthesize 68Ga-labeled PSMA inhibitor (68Ga-PSMA-11) with semi-automated module and to evaluate its biodistribution and kinetics in normal mice. Methods A total of 5 μg PSMA-11 was added into 4 ml GaCl3 elute (185-555 MBq), and the pH value was adjusted to 4.0. The mixture was reacted at room temperature (RT) or 90 ℃ for 10 min. The radiochemical purity and yield were analyzed by HPLC, and its stability in vitro was evaluated. Cell uptake was detected on 22RV1 and PC-3 cells. The biodistribution and kinetics were evaluated by the dissection method and dynamic imaging with microPET/CT in normal and tumor-bearing mice. ROI analysis was performed, TAC was processed in main organs. Results The radiochemical purity of 68Ga-PSMA-11 was higher than 99%. The radio-yield was (95±2)% in module(90 ℃), whereas (89±3)% at RT. The uptake of 68Ga-PSMA-11 by PSMA-positive 22RV1 cells was significantly higher than that of PSMA-negative PC-3 cells. 68Ga-PSMA-11 in blood was cleared rapidly, it was mainly excreted by the kidneys. Some radioactive uptake was found in the liver and intestine; and less radioactive uptake in lungs. MicroPET/CT imaging showed that 68Ga-PSMA-11 had a good affinity to PSMA-positive tumors. Further study showed that Tβ1/2 was shorter when 68Ga-PSMA-11 was labeled at 90 ℃. Conclusions 68Ga-PSMA-11 could present good biodistribution and rapid blood clearance in mice, thus it could be a promising PSMA targeting imaging agent. 68Ga-PSMA-11 labeled at 90 ℃ has higher yield and faster blood clearance. Key words: Prostate-specific antigen; Isotope labeling; Gallium radioisotopes; Tomography, emission-computed; Tomography, X-ray computed; Tumor cells, cultured; Mice