环戊二烯基三羰基锰族放射性分子影像探针的设计与合成

99mTc, 188Re and 186Re are most important isotopes of manganese triad in radiopharmaceutical probes. However, their application as radiopharmaceuticals are only limited within the range of simple coordination compounds.Recent development in organometallic chemistry has shown that organometallic compounds containing cyclopentadienyl manganese triad derivatives exhibit strong interaction with many receptors in biosystem, implying that the organometallic compounds like cyclopentadienyl 99mTc (188Re, 186Re) may most probably break through the bottle neck for the developing of the new type of radiopharmaceutical probes. The challenging scientific problem is how to prepare these organometallic compounds in aqueous condition. This problem is proposed to be tackled in this application from the following two aspects, (1) taking the amino acid receptor as target, the methods and paths for the preparation of organometallic derivatives containing cyclopentadienyl triscarbonyl manganese (rhenium) in aqueous are to be explored; (2) Based upon the realization and experience of syntheses of organometallic derivatives of cyclopentadienyl triscarbonyl manganese (rhenium) in aqueous condition, the method for preparing the corresponding organometallic radiopharmaceuticals containing 99mTc and 188Re is to be provided and imaging experiment will be further carried out with the advent of these organometallic compounds.

锰族元素中的99mTc 、188Re和186Re 是放射性探针药物研究中十分重要的核素，但它们的使用仍只局限于简单的配位化合物。金属有机化学最新进展表明环戊二烯三羰基锰族衍生物与一些生物受体有着很强的相互作用，预示金属有机化合物，如环戊二烯三羰基99mTc(188Re，186Re)等衍生物的合成极有可能突破放射性探针药物发展的瓶颈。如何在有水有氧的药物使用环境中合成这类有机金属化合物成为一个具有挑战性的科学问题。本课题将通过对以下两方面着手来对上述问题进行探索性研究：（1）以氨基酸受体为靶标，探索在水相中合成环戊二烯三羰基锰（铼）的金属有机衍生物的方法和路径；（2）在实现水相合成含有环戊二烯三羰基锰（铼）的金属有机衍生物的基础上，水相合成188Re/99mTc 金属有机放射性探针化合物（Organometallic Radiopharmaceutical），进行相应的的核成像实验。

本研究针对水相的三羰基锰金属有机化学，制备了一系列具有不同取代基团的环戊二烯三羰基锰的金属有机衍生物；采用新方法制备了环戊二烯二聚体，并成功在水相环境下制备了锝-99m标记的环戊二烯甲酸三羰基锝；首次在室温、水相环境下成功制备了三羰基锝-99m中间体（[99mTc(H2O)3(CO)3]+），与现有的方法相比，原料易得，操作简便，省去了加热环节，对三羰基锝-99m放射性药物的研发和应用提供了一种新方法。此外进一步扩展99mTc标记探针的研究范围，成功的制备了锝-99m及羰基锝-99m标记的秋水仙碱、美法仑及氨基葡萄糖等肿瘤分子探针，并对其生物性能进行了初步的研究。