68Ga-PSMA-11标记合成及生物分布和代谢动力学研究

摘要

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 μgPSMA-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.ROl 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.%目的 利用合成模块,建立68Ga标记合成PSMA抑制剂PSMA-11的新方法,研究其生物分布及代谢动力学特征.方法 向4ml含185～555 MBq GaCl3溶液中加入5μg PSMA-11,调节pH值至4.0,常温或90℃反应10 min,HPLC检测其放化纯、产率,评价68Ga-PSMA-11的体外稳定性.利用22RV 1和PC-3细胞考察肿瘤细胞与其结合能力.MicroPET/CT动态显像及解剖观察68Ga-PSMA-11在正常小鼠及荷瘤鼠体内的生物分布.勾画ROI,获得血液、肿瘤和各主要脏器的TAC,并考察其在血液中的代谢动力学特点.结果 常温或90℃反应条件下,产物放化纯均在99％以上;90℃加热时未校正的产率为(95±2)％,高于常温时的(89±3)％.PSMA阳性的22RV1细胞对该标记化合物的摄取明显高于PSMA阴性的PC-3细胞.68Ga-PSMA-11血液清除快,主要经肾脏排泄,肠道有部分放射性摄取,肝脏和肺放射性摄取少.MicroPET/CT显像示,68Ga-PSMA-11对PSMA阳性肿瘤有很好的靶向性.加热条件下清除半衰期更短.结论 68Ga-PSMA-11的生物分布理想、血液清除快,主要经肾脏排泄,小肠、肝、肺放射性摄取很少,清除很快,是优良的PSMA靶向显像剂.加热条件下制备的68Ga-PSMA-11产率更高、血液清除更快.