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[18F]Flurpiridaz: Facile and Improved Precursor Synthesis for this Next-Generation Cardiac Positron Emission Tomography Imaging Agent |
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| Authors: | Dr Hazem Ahmed Dr Ahmed Haider Livio Gisler Prof Roger Schibli Prof Catherine Gebhard Prof Simon M Ametamey |
| Affiliation: | 1. Institute of Pharmaceutical Sciences Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland;2. Department of Nuclear Medicine, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, 8952 Schlieren, Switzerland |
| Abstract: | 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. |
| Keywords: | flurpiridaz imaging agents myocardial perfusion imaging positron emission tomography synthetic methods |