Medicinal Inorganic Chemistry Group, Department of Chemistry, The University of British Columbia, Vancouver, BC, Canada.
Nucl Med Biol. 2011 Nov;38(8):1165-74. doi: 10.1016/j.nucmedbio.2011.05.004. Epub 2011 Aug 9.
Recent advances in positron emission tomography (PET)/computed tomography have fueled the development of new PET-isotope-based agents for myocardial perfusion imaging. (68)Ga, a generator-produced PET isotope, is an attractive radionuclide for developing a (68)Ga-based cardiac imaging agent. We have synthesized seven new chelate systems based on our previously reported 1,2-[{6-(carboxylato-)pyridin-2-yl}methylamino]ethane (H(2)dedpa) scaffold. These ligands form lipophilic, cationic complexes upon coordination of (67/68)Ga(III) under mild, direct labeling conditions within 10 min at room temperature. The corresponding cold complexes were also synthesized, and the solid-state structure of one of the complexes, [Ga(19)][ClO(4)], was determined. All compounds were investigated for in vitro stability against transferrin, and log P values were determined. In vivo biodistribution studies in mice showed that four of the seven investigated complexes provided greatly improved blood, lung and kidney clearance compared to previously reported derivatives. Two complexes with log P>1.1 exhibited persistent heart uptake over the course of 2 h above 1% ID/g.
近年来，正电子发射断层扫描（PET）/计算机断层扫描的发展推动了基于新型 PET 同位素的心肌灌注成像试剂的研发。（68）Ga 是一种发生器生产的 PET 同位素，是开发基于（68）Ga 的心脏成像试剂的有吸引力的放射性核素。我们已经合成了七种基于我们之前报道的 1,2-[[6-（羧基）吡啶-2-基]甲基氨基]乙烷（H（2）dedpa）支架的新型螯合系统。这些配体在温和的直接标记条件下，在室温下 10 分钟内形成亲脂性、阳离子络合物，配位（67/68）Ga（III）。还合成了相应的冷配合物，并确定了其中一种配合物[Ga（19）][ClO（4）]的固态结构。所有化合物均进行了针对转铁蛋白的体外稳定性研究，并测定了 log P 值。在小鼠体内生物分布研究中，与之前报道的衍生物相比，七种研究的配合物中的四种提供了大大改善的血液、肺和肾脏清除率。两个 log P 值大于 1.1 的配合物在 2 小时以上的过程中，心脏摄取率持续超过 1% ID/g。
