靶向前列腺特异性膜抗原药物68Ga-SC691两种前列腺癌小鼠模型micro-PET/CT比较研究

micro-PET/CT comparative study of drug 68Ga-SC691 targeting PSMA in two animal models with prostate cancer

目的 比较分析靶向前列腺特异性膜抗原(PSMA)的新型特异性分子探针在不同放射生物模型中的特性,以寻求评估此类放射性药物的合理生物模型。方法 采用人源性前列腺癌细胞LNCaP、22RV1对靶向PSMA诊断的药物68Ga-SC691进行体外细胞摄取内化实验,测定及比较分析2种细胞对68Ga-SC691的结合能力。采用SPF级别NOD/SCID鼠建立LNCaP、22RV1荷瘤鼠模型,经尾静脉注射68Ga-SC691后进行生物分布和小动物PET/CT成像研究,计算并比较肿瘤、肾脏、血液和各主要脏器的摄取值。结果 体外结合实验显示,LNCaP细胞对68Ga-SC691的摄取高于22RV1细胞,在孵育2 h后,(46.01±2.43)%细胞摄取,22RV1细胞摄取为(2.20±0.58)%,t=22.62,P=0.000 1。小鼠体内分布结果表明,标记物主要经肾脏代谢,2种生物模型药代动力学特点类似,但在LNCAP荷瘤鼠肿瘤部位有更高的放射性摄取,在药物注射30 min时,其放射性摄取值在LNCaP模型中为(43.41±8.39)%ID/g,在22RV1模型中为(1.71±0.51)%ID/g,且显像效果优于使用22RV1模型。结论68Ga-SC691在生物模型LNCaP和22RV1中有不同程度的摄取,LNCaP模型对靶向PSMA前列腺癌显像评价效果优于22RV1模型,有利于PSMA靶向药物的开发与评价,利于后续临床工作的开展。

Objective To find a more appropriate biological model for studying new PSMA-targeted radiotracers by comparing and analyzing the characteristics of these radiotracers in different biological models.Methods The human-derived prostate cancer cell LNCaP and 22RV1 were used for in vitro cell uptake and internalization experiments with the PSMA-targeted tracer68Ga-SC691,and the binding ability of the two cell lines was determined and compared.LNCaP and 22RV1 xenografts models were established by using SPF NOD/SCID mice.The biodistribution and micro-PET/CT imaging were studied in the LNCaP xenograft model and 22RV1 xenograft model after a caudal vein injection of68Ga-SC691,and uptake values of the tumor, kidney, blood and other major organs were calculated.Results In vitro binding experiments showed that the uptake of68Ga-SC691 by LNCaP cells was significantly higher than that of 22RV1 cells [(46.01±2.43)% in LNCaP cell vs(2.20±0.58)% in 22RV1 cells after 2 h incubation, t=22.62,P=0.000 1].Biodistribution studies showed that68Ga-SC691 was mainly excreted via the renal pathway.The pharmacokinetic characteristics of the two biological models were similar.However, there was a significantly higher uptake in the tumor site of LNCaP-bearing mice[(43.41±8.39)%ID/g in LNCaP modell vs(1.71±0.51)%ID/g in 22RV1model after 30min p.i.].In addition,better imaging quality was observed for the LNCaP model.Conclusions This article systematically evaluated the uptake of 68 GaSC691in two often-used biological models of LNCaP and 22RV1,and the results showed that they had different levels of uptake.The LNCaP model is better than the 22RV1model in terms of the uptake and micro-PET/CT imaging for evaluating radiotracers that target PSMA-positive prostate cancer.