Yazdani Abdolreza, Janzen Nancy, Czorny Shannon, Valliant John F
Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario L8S 4M1, Canada.
Inorg Chem. 2017 Mar 6;56(5):2958-2965. doi: 10.1021/acs.inorgchem.6b03058. Epub 2017 Feb 15.
Bathophenanthrolinedisulfonate (BPS) complexes of technetium(I) of the type [Tc(CO)(BPS)(L)] (L = imidazole derivatives) were synthesized and evaluated both in vitro and in vivo. [Tc(CO)(BPS)(MeIm)] (MeIm = 1-methyl-1H-imidazole) was prepared in near-quantitative yield using a convenient two-step, one-pot labeling procedure. A targeted analogue capable of binding regions of calcium turnover associated with bone metabolism was also prepared. Here, a bisphosphonate was linked to the metal through an imidazole ligand to give [Tc(CO)(BPS)(ImAln)] (ImAln = an imidazole-alendronate ligand) in high yield. The technetium(I) complexes were stable in vitro, and in biodistribution studies, [Tc(CO)(BPS)(ImAln)] exhibited rapid clearance from nontarget tissues and significant accumulation in the shoulder (7.9 ± 0.2% ID/g) and knees (15.1 ± 0.9% ID/g) by 6 h, with the residence time in the skeleton reaching 24 h. A rhenium analogue, which is luminescent and has the same structure, was also prepared and used for fluorescence labeling of cells in vitro. The data reported demonstrate the potential of this class of compounds for use in creating isostructural optical and nuclear probes.
合成了[Tc(CO)(BPS)(L)]（L = 咪唑衍生物）类型的锝（I）的二磺酸二氮杂菲配合物（BPS），并进行了体外和体内评估。使用便捷的两步一锅法标记程序，以近乎定量的产率制备了[Tc(CO)(BPS)(MeIm)]（MeIm = 1-甲基-1H-咪唑）。还制备了一种能够结合与骨代谢相关的钙周转区域的靶向类似物。在此，通过咪唑配体将双膦酸盐与金属相连，以高产率得到[Tc(CO)(BPS)(ImAln)]（ImAln = 咪唑-阿仑膦酸盐配体）。锝（I）配合物在体外稳定，在生物分布研究中，[Tc(CO)(BPS)(ImAln)]在6小时时从非靶组织中快速清除，并在肩部（7.9±0.2% ID/g）和膝盖（15.1±0.9% ID/g）中显著积累，在骨骼中的停留时间达到24小时。还制备了一种具有发光性且结构相同的铼类似物，并将其用于体外细胞的荧光标记。所报道的数据证明了这类化合物在创建同构光学和核探针方面的应用潜力。
