^(99)Tc^m-MAVGG-硝基咪唑硫嘌呤荷瘤小鼠乏氧显像

Experimental study of tumor hypoxia imaging with ^(99)Tc^m-MAVGG-azathiopurine in vitro and in vivo

目的探讨有氧与乏氧条件下^(99)Tc^m-巯基乙酰基-缬氨酸-甘氨酸-甘氨酸(MAVGG)-硝基咪唑硫嘌呤在肿瘤细胞的摄取及其在荷瘤小鼠体内的生物学分布和显像特点。方法用^(99)Tc^m标记双功能螯合剂 MAVGG 偶联的硝基咪唑硫嘌呤。体外测定有氧与乏氧条件下标记物在 S180肉瘤细胞内的滞留率。观察荷瘤小鼠体内生物学分布及其γ显像。结果乏氧条件下标记物与 S180肉瘤细胞结合5 h 后,在 S180肉瘤细胞内的滞留率为0.59,高于有氧条件下的0.36。生物学分布显示肿瘤摄取率高,注射后3 h 肿瘤与肌肉和血液的摄取率比值分别为4.24和1.55。γ显像示肿瘤显影清晰。结论 ^(99)Tc^m-MAVGG-硝基咪唑硫嘌呤有望作为新的肿瘤乏氧显像剂。

Objective To investigate the biodistribution and scintigraphy of ^99Tc^m-mercaptoacetyl- Val-Gly-Gly-（MAVGG）-azathiopurine in hypoxic mice tumors （S180） in vivo. Methods Azathiopurine was radiolabelled with 99Tcm via the bifunctional chelator MAVGG. Cell accumulation was studied in S180 cells under hypoxic condition and compared with oxygenous condition. The results were expressed as an accumulation ratio, Cin/Cout, defined as concentration of radioactivity within the cells divided by that in the external medium. Biodistribution and scintigraphy in S180 tumor bearing mice were studied at different time point post injection of ^99Tc^m-MAVGG-azathiopruine. Results At 5 h after injection, the Cin/Cout was 0. 59 for hypoxia and 0.36 for oxygenation. The biodistribution was 4.24 for tumor-to-muscle and 1.55 for tumor-to-blood at 3 h post-injection. The results were showed in scintigraphic images. Conclusion Retention of ^99Tc^m-MAVGG-azathiopurine was 1.6 fold higher in hypoxic than in oxygenous condition, suggesting this compound might possibly be a candidate for tumor hypoxic imaging agent.