Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Int J Pharm. 2012 Jan 17;422(1-2):418-27. doi: 10.1016/j.ijpharm.2011.10.036. Epub 2011 Oct 21.
Currently, in vivo or in vitro(99m)Tc-radiolabelled red blood cells are the standard blood pool imaging agents. Due to risks associated with handling of blood and the problems with the current (99m)Tc shortage, we were interested in a long-circulating biocompatible synthetic macromolecule that would be simple to prepare and could also be used for PET imaging.
A high molecular weight hyperbranched polyglycerol (HPG) of 500 kDa was derivatized to coordinate radioactive gallium and to establish its labelling efficiency, stability and pharmacokinetics.
The resulting radiopharmaceutical in kit form was labelled rapidly within a couple of minutes at room temperature, was stable in transferrin and EDTA challenge tests, and was non-toxic in both cell viability and different hemocompatibility assays. A pharmacokinetic biodistribution study showed that the (67)Ga-HPGN was confined to the blood compartment with a biological half life of 50.7h.
(67)Ga-HPGN is thus a simple to prepare blood pool imaging agent for applications where a long biological half-life is essential, i.e., the diagnosis of internal bleeding. Since radiolabelling of the same kit with (68)Ga was also confirmed, we plan to evaluate it shortly as a PET blood pool imaging agent for cardiac applications.
目前，体内或体外（99m）Tc 放射性标记的红细胞是标准的血池成像剂。由于与血液处理相关的风险以及当前（99m）Tc 短缺的问题，我们对一种具有长期循环、生物相容性的合成大分子感兴趣，这种大分子既易于制备，也可用于 PET 成像。
将高分子量的超支化聚甘油（HPG）衍生化以与放射性镓配位，并确定其标记效率、稳定性和药代动力学。
试剂盒形式的放射性药物在室温下可在几分钟内快速标记，在转铁蛋白和 EDTA 挑战测试中稳定，在细胞活力和不同血液相容性测定中均无毒。药代动力学生物分布研究表明，（67）Ga-HPGN 局限于血液隔室，生物半衰期为 50.7h。
因此，（67）Ga-HPGN 是一种简单的血池成像剂，适用于需要长生物半衰期的应用，例如，内部出血的诊断。由于相同试剂盒的（68）Ga 放射性标记也得到了证实，我们计划尽快将其评估为心脏应用的 PET 血池成像剂。
