乏氧显像剂<sup>99</sup>Tc<sup>m-</sup>HL91衍生物的制备及其活性评价

乏氧显像剂⁹⁹Tc^m-HL91衍生物的制备及其活性评价

摘要: 为寻找性能优良的乏氧显像剂，设计合成了2种HL91衍生物4, 9-二氮-3, 10-二甲基十二烷-2, 11-二酮肟 (TMBAO)和4, 9-二氮-3, 10-二氧基十二烷-2, 11-二酮肟 (H₂Pab)，并进行⁹⁹Tc^m标记。与已知乏氧显像剂⁹⁹Tc^m-HL91进行比较，并对新标记物的体内外活性进行了评价。乏氧细胞实验结果表明：与⁹⁹Tc^m-HL91相比，⁹⁹Tc^m-TMBAO和⁹⁹Tc^m-H₂Pab具有一定的乏氧选择性；荷瘤小鼠体内生物分布数据显示，尽管两种新的⁹⁹Tc^m标记物在肝脏的摄取比⁹⁹Tc^m-HL91低，但其乏氧选择性也同时显著降低。

Abstract: In order to find the optimum hypoxia imaging agent, two derivatives of HL91－4, 9-diaza-3, 10-dimethyl-dodecane-2, 11-dione dioxime (TMBAO) and N, N’-bis (2-hydroxyimino propionyl)-1, 4-diaminobutane(H₂Pab)—were synthesized and labeled with ⁹⁹Tc^m. Evaluation of these complexes as tumor hypoxia markers were performed both in vitroand in vivocompared with ⁹⁹Tc^m-HL91—a putative hypoxic tracer. The tumor cell experiment and the biodistribution in mice bearing EMT-6 tumor show that the two derivatives—⁹⁹Tc^m-TMBAO and ⁹⁹Tc^m-H₂Pab have less hypoxic selectivity than ⁹⁹Tc^m-HL91 in despite of their lower liver uptake.