新型乏氧肿瘤显像剂^(99)Tc^m-MNLS、^(99)Tc^m-MLS的合成及其在小鼠体内的生物分布  

Preparation of Hypoxic Imaging Agents ^(99)Tc^m-MNLS and ^(99)Tc^m-MLS and Their Biodistribution in Mice

作　　者：查智豪[1] 汪建军[1] 朱霖[1] 

机构地区：[1]北京师范大学化学学院放射性药物教育部重点实验室,北京100875

出　　处：《同位素》2009年第4期197-203,共7页Journal of Isotopes

基　　金：北京师范大学放射性药物教育部重点实验室2007年开放基金资助项目(0511);高等学校博士学科点专项科研基金资助项目(20040027011)

摘　　要：合成了含有硝基咪唑基团的磷酸酯衍生物2-(2-methyl-5-nitro-1H-imidazol-1-yl)Ethyl DihydrogenPhosphate(MNLS)和它的非硝基类似物2-(2-methyl-1H-imidazol-1-yl)Ethyl Dihydrogen Phosphate(MLS),采用99Tcm直接法对其进行标记,并研究了99Tcm-MNLS和99Tcm-MLS的理化性质及其在荷EMT-6小鼠体内的生物分布。采用最佳标记条件后,99Tcm-MNLS和99Tcm-MLS的标记率均>90%。荷EMT-6小鼠体内生物分布表明:99Tcm-MNLS的肿瘤放射性摄取率、肿瘤与肌肉和肿瘤与肝的放射性摄取比(T/NT)(120 min时分别为2.99±0.25%ID/g、5.90和1.03)显著高于已知的乏氧显像剂99Tcm-HL91(120 min时分别为0.93±0.13%ID/g、3.59和0.17)和不含硝基基团的类似物99Tcm-MLS(120 min时分别为1.61±0.13%ID/g、5.40和0.13)。与99Tcm-MLS相比,99Tcm-MNLS配体中的硝基对于肿瘤的摄取影响很大,这表明99Tcm-MNLS的肿瘤摄取与其乏氧机制有关。上述研究结果表明,99Tcm-MNLS具有肝摄取低,肿瘤摄取较高的优点,作为潜在的新型乏氧肿瘤显像剂,值得进一步研究。To develop ^99Tc^m labeled hypoxic agents, two phosphate-based chelating agents were coupled to metronidazole, 2-（2-methyl-5-nitro-lH-imidazol-1-yl） ethyl dihydrogen phosphate （MNLS） and its analog 2-（2-methyl-1H-imidazol-1-yl）ethyl dihydrogen phosphate（MLS）were synthesized based on the mechanism of prodrug. Labeling yield of these ^99 Tc^m complexes were more than 90% as proved by TLC. Paper electrophoresis showed that these complexes were neutral. Biodistribution of these complexes in tumor-bearing mice showed that the uptake of ^99Tc^m-MNLS （120 min, 2.99±0.25 ID%/g） in tumor was higher than that of ^99Tc^m-HL91（120 min, 0.93±0.13 ID%/g） and ^99Tc^m-MLS（120 min, 1.61 ±0.13 ID%/g）, and the uptake ratio of tumor to muscle and tumor to liver of ^99Tc^m -MNLS （120 min, 5.90, 1.03） were higher than that of ^99Tc^m-HL91（120 min, 3. 59, 0. 17） and ^99Tc^m-MLS（120 min, 5.40, 0.13）. The higher tumor uptake for ^99Tc^m-MNLS than ^99Tc^m- MLS suggested that nitroimidazole was a key group for tumor accumulation. ^99Tc^m-MNLS had higher tumor uptake and lower liver uptake, which had the potential for tumor imaging and was worth of further vestigation.

关 键 词：^99TC^M 乏氧组织显像剂 生物分布 

分 类 号：R817[医药卫生—影像医学与核医学]