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

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 Dihydrogen Phosphate（MNLS）和它的非硝基类似物2-（2-methyl-1H-imidazol-l-yl）Ethyl Dihydrogen Phosphate（MLS），采用^99Tc^m直接法对其进行标记，并研究了^99Tc^m-MNLS和^99Tc^m-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，^99Tc^m-MNLS和^99Tc^m-MLS的标记率均〉90％。荷EMT-6小鼠体内生物分布表明：^99Tc^m-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）（120min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^99Tc^m-HL91（120min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^99Tc^m-MLS（120min时分别为1．61±0．13％ID／g、5．40和0．13）。与^99Tc^m-MLS相比^99Tc^m-MNLS配体中的硝基对于肿瘤的摄取影响很大，这表明^99Tc^m-MNLS的肿瘤摄取与其乏氧机制有关。上述研究结果表明，^99Tc^m-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。

Preparation of Hypoxic Imaging Agents 99Tcm-MNLS and 99Tcm-MLS and Their Biodistribution in Mice

To develop 99Tcm labeled hypoxic agents, two phosphate-based chelating agents were coupled to metronidazole, 2-(2-methyl-5-nitro-1H-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 99Tcm 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 99Tcm-MNLS (120 min, 2.99±0.25 ID%/g) in tumor was higher than that of 99Tcm-HL91(120 min, 0.93±0.13 ID%/g) and 99Tcm-MLS(120 min, 1.61±0.13 ID%/g), and the uptake ratio of tumor to muscle and tumor to liver of 99Tcm-MNLS (120 min, 5.90， 1.03) were higher than that of 99Tcm-HL91(120 min, 3.59， 017) and 99Tcm-MLS(120 min, 5.40， 0.13）. The higher tumor uptake for 99Tcm-MNLS than 99Tcm-MLS suggested that nitroimidazole was a key group for tumor accumulation. 99Tcm-MNLS had higher tumor uptake and lower liver uptake, which had the potential for tumor imaging and was worth of further vestigation.