乏氧组织显像剂99Tcm-DTPA-甲硝唑的制备和荷瘤动物实验研究

目的　进行新型乏氧组织显像剂DTPA 甲硝唑的化学合成、药盒制备、99Tcm 标记、质量控制以及药理研究。方法　合成的DTPA 甲硝唑用氯化亚锡作还原剂 ,99Tcm 标记 ,用多元正交法确立99Tcm 标记一步法药盒的最佳配方。纸层析法鉴定99Tcm DTPA 甲硝唑的标记率、标记稳定性 ,完成了H2 2肝癌小鼠体内生物分布实验及显像研究。结果　DTPA 甲硝唑一步法药盒与99TcmO-4 混合 ,沸水浴反应 10min ,放化纯度大于 99%。H2 2肝癌小鼠生物分布显示 ,肿瘤 /血液比值 1、2h分别为3 43、6 40 ,肿瘤 /肌肉比值 1、2h分别为 5 2 4、7 42 ;注射血管舒张药肼苯哒嗪组肿瘤组织摄取明显高于对照组 (P <0 0 1)。结论　研制的99Tcm DTPA 甲硝唑有望成为一种新型的肿瘤乏氧组织显像剂。

Preparation and experimental study of 99 Tcm-DTPA-metronidazole for imaging tumor hypoxia

Objective The development of a novel tissue hypoxia imaging agent, 99 Tc m DTPA metronidazole (MTZ),has been described here Methods DTPA MTZ was synthesized, labeled with 99 Tc m by a stannous chloride reduction method The radiochemical purity was determined by paper chromatography The biodistribution study and whole body gamma scintigraphic imaging with hepatoma 22 (H22) bearing mice were fulfilled Results The kit formation has been developed using the synthetic product 99 Tc m DTPA MTZ could be prepared by adding pertechnetate into the DTPA MTZ kit and let react for 10 min in boiling water bath and showed high radiochemical purity of 99% High tumor/blood ratios (3 43, 6 40 by 1, 2 h) and tumor/muscle ratios (5 24, 7 42 by 1, 2 h) were observed Hydralazine which affects blood flow and increases hypoxic cell fraction in tumors significantly increased levels of 99 Tc m DTPA MTZ radioactivity over control levels(P<0 01) Conclusion 99 Tc m DTPA MTZ is a potential agent to be used for imaging tumor hypoxia in the laboratory or clinic