Long-circulating non-toxic blood pool imaging agent based on hyperbranched polyglycerols
Long-circulating non-toxic blood pool imaging agent based on hyperbranched polyglycerols
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DOI：
10.1016/j.ijpharm.2011.10.036
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发表时间：
2012-01-17
影响因子：
5.8
通讯作者：
Haefeli, Urs O.
中科院分区：
文献类型：
--
作者：
Saatchi, Katayoun;Gelder, Nikolaus;Haefeli, Urs O.
目的：目前，体内或体外Tc-99 m标记的红细胞是标准的血池显像剂。由于与血液处理相关的风险和当前Tc-99 m短缺的问题，我们对制备简单且也可用于PET成像的长循环生物相容性合成大分子感兴趣。方法：将500 kDa的高分子量超支化聚甘油（HPG）衍生化以配位放射性镓并确定其标记效率，结果：所得到的试剂盒形式的放射性药物在室温下在几分钟内被快速标记，在转铁蛋白和EDTA挑战试验中是稳定的，并且在细胞活力和不同的血液相容性测定中是无毒的。药代动力学生物分布研究显示Ga-67-HPGN局限于血液隔室，生物半衰期为50.7小时。结论：Ga-67-HPGN因此是制备血池成像剂的简单方法，用于其中长生物半衰期是必需的应用，即，内出血的诊断。由于用Ga-68对相同试剂盒进行放射性标记也得到了证实，我们计划很快将其作为PET血池显像剂用于心脏应用。(C)2011 Elsevier B. V.保留所有权利。
Purpose: Currently, in vivo or in vitro Tc-99m-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 Tc-99m 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.Methods: 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.Results: 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 Ga-67-HPGN was confined to the blood compartment with a biological half life of 50.7 h.Conclusion: Ga-67-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 Ga-68 was also confirmed, we plan to evaluate it shortly as a PET blood pool imaging agent for cardiac applications. (C) 2011 Elsevier B.V. All rights reserved.