[18 F]Flurpiridaz: Facile and Improved Precursor Synthesis for this Next-Generation Cardiac Positron Emission Tomography Imaging Agent.
Hazem AhmedAhmed HaiderLivio GislerRoger SchibliCatherine GebhardSimon M AmetameyPublished in: ChemMedChem (2020)
[18 F]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 [18 F]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 [18 F]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.
Keyphrases
- positron emission tomography
- blood flow
- phase iii
- coronary artery disease
- clinical trial
- computed tomography
- left ventricular
- cardiovascular disease
- open label
- pet imaging
- phase ii
- pet ct
- mouse model
- high resolution
- double blind
- cardiovascular events
- heart failure
- percutaneous coronary intervention
- mental health
- physical activity
- oxidative stress
- quantum dots
- coronary artery
- aortic stenosis
- type diabetes
- coronary artery bypass grafting
- placebo controlled
- reduced graphene oxide
- gold nanoparticles
- metabolic syndrome
- binding protein
- ejection fraction
- high speed