两种新型^(99m)TcN核标记的甲硝唑类乏氧显像剂的制备及生物性能评价

Preparation and Biological Evaluation of Two Novel ^(99m)Tc-nitrido Complexes of Metronidazole Derivative for Targeting Hypoxia

为研制新的肿瘤乏氧显像剂,设计合成了2-(2-甲基-5-硝基咪唑基)乙基氨荒酸钾(MNIE-DTC)和4-(2-甲基-5-硝基咪唑基)丁基氨荒酸钾(MNIB-DTC)两种氨荒酸盐配体,并制得了相应的99mTcN核配合物99mTcN(MNIE-DTC)2和99mTcN(MNIB-DTC)2.所获得的两种99mTcN核配合物均为电中性,具有较高的体外稳定性.在荷乳腺癌的TA-2小鼠体内分布实验结果显示,两种配合物均具有一定的肿瘤摄取,给药1h后,99mTcN(MNIE-DTC)2和99mTcN(MNIB-DTC)2的肿瘤摄取率分别为(0.50±0.01)%ID/g和(0.64±0.10)%ID/g.注入肼苯哒嗪后,两种配合物的肿瘤摄取明显增高,表明这两种配合物都具有对乏氧肿瘤的选择性.

In order to develop new tumor hypoxia imaging agent, two novel dithiocarbamate ligands, potassi- um 2- （ 2-methyl-5-nitro-1 H-imidazolyl） -ethyl-earbamate （ MNIE-DTC ） and potassium 4- （ 2-methyl-5-nitro-1 H- imidazolyl）-butyl-carbamate （MNIB-DTC）, and the corresponding ^99mTcN-eomplexes were prepared. Both neutral complexes were stable in vitro. Biological evaluation in TA-2 mice bearing MA891 tumor showed that both [ ^99mTeN （MNIE-DTC） 2 3 and [ ^99mTcN （MNIB-DTC） 2 ] had certain tumor uptakes of （0. 50 ± 0.01 ） % ID/g and （0. 64 ± 0. 10）% ID/g at 1 h post-injection, respectively. A significant increase in tumor uptakes of both complexes were produced by injection of hydralazine. The results indicated that the two complexes could be selectively accumulated in hypoxic tumors.