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[18 F]Flurpiridaz: Facile and Improved Precursor Synthesis for this Next-Generation Cardiac Positron Emission Tomography Imaging Agent.
ChemMedChem ( IF 3.4 ) Pub Date : 2020-04-23 , DOI: 10.1002/cmdc.202000085
Hazem Ahmed 1 , Ahmed Haider 2, 3 , Livio Gisler 1 , Roger Schibli 1 , Catherine Gebhard 2, 3 , Simon M Ametamey 1
Affiliation  

[18F]Flurpiridaz is a recently developed positron emission tomography tracer that is currently being investigated in phase III clinical trials to measure myocardial blood flow. The relatively long physical half‐life of fluorine‐18 alongside the high spatial resolution and outstanding myocardium‐to‐background ratio fuels its potential to be the next gold standard for the early detection of coronary artery disease. Notwithstanding the expected widespread use of [18F]flurpiridaz, the reported multistep synthesis of its precursor for radiofluorination involves a hazardous alkylation step using carcinogenic ethylene oxide, and a low overall chemical yield of 7 %. In this work, we have improved the overall yield more than fivefold and concurrently replaced the hazardous step. Specificity of binding of [18F]flurpiridaz to mitochondrial complex 1 was demonstrated by in vitro autoradiography on mouse heart tissue sections. These results thus pave the way for assessing myocardial blood flow and coronary flow reserve in mouse models of cardiovascular disease.

中文翻译:

[18 F] Flurpiridaz:方便的和改进的前体合成,用于这种下一代心脏正电子发射断层显像成像剂。

[ 18 F] Flurpiridaz是最近开发的正电子发射断层显像示踪剂,目前正在III期临床试验中进行研究以测量心肌血流量。氟18相对较长的物理半衰期,以及较高的空间分辨率和出色的心肌与背景比,使其有可能成为早期发现冠状动脉疾病的下一个金标准。尽管[ 18F] flurpiridaz是已报道的用于放射性氟化的前体的多步合成方法,涉及使用致癌性环氧乙烷的危险烷基化步骤,总化学收率较低,为7%。在这项工作中,我们将总产量提高了五倍以上,同时取代了危险步骤。[ 18 F]氟吡唑与线粒体复合物1的结合特异性已通过体外放射自显影在小鼠心脏组织切片上得到证实。因此,这些结果为评估心血管疾病小鼠模型中的心肌血流和冠状动脉血流储备铺平了道路。
更新日期:2020-06-23
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