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J Labelled Comp Radiopharm. 2020 Jan 9. doi: 10.1002/jlcr.3827. [Epub ahead of print]

Efficient radiosynthesis and preclinical evaluation of [18 F]FOMPyD as a PET tracer candidate for TrkB/C receptor imaging.

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McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
Department of Oncology, Division of Oncological Imaging, University of Alberta, Edmonton, AB, Canada.
Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, Douglas Mental Health University Institute, Montreal, QC, Canada.


Herein we report an efficient radiolabeling of a 18 F-fluorinated derivative of dual inhibitor GW2580, with its subsequent evaluation as a positron emission tomography (PET) tracer candidate for imaging of two neuroreceptor targets implicated in the pathophysiology of neurodegeneration: tropomyosin receptor kinases (TrkB/C) and colony stimulating factor receptor (CSF-1R). [18 F]FOMPyD was synthesized from a boronic acid pinacolate precursor via copper-mediated 18 F-fluorination concerted with thermal deprotection of the four Boc groups on a diaminopyrimidine moiety in an 8.7±2.8% radiochemical yield, a radiochemical purity >99% and an effective molar activity of 187±93 GBq/μmol. [18 F]FOMPyD showed moderate brain permeability in wild-type rats (SUVmax = 0.75) and a slow washout rate. The brain uptake was partially reduced (ΔAUC40-90 = 11.6%) by administration of the non-radioactive FOMPyD (up to 30 μg/kg). In autoradiography, [18 F]FOMPyD exhibits ubiquitous distribution in rat and human brain tissues with relatively high non-specific binding revealed by self-blocking experiment. The binding was blocked by TrkB/C inhibitors, but not with a CSF-1R inhibitor, suggesting selective binding to the former receptor. Although an unfavorable pharmacokinetic profile will likely preclude application of [18 F]FOMPyD as a PET tracer for brain imaging, the concomitant one-pot copper-mediated 18 F-fluorination/Boc-deprotection is a practical technique for the automated radiosynthesis of acid-sensitive PET tracers.


Brain imaging; GW2580; PET; [18F]FOMPyD; colony stimulating factor receptor (CSF-1R); copper-mediated 18F-fluorination; fluorine-18; positron emission tomography; tropomyosin receptor kinase (Trk)


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