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

Herein we report an efficient radiolabeling of a18F ‐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 fa ctor receptor (CSF‐1R). [18F]FOMPyD was synthesized from a boronic acid pinacolate precursorvia copper ‐mediated18F ‐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. [18F]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, [18F]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 [18F]FOMPyD as a PET tracer for brain imaging, the concomitant one ‐pot copper‐mediated18F ‐fluorination/Boc‐deprotection is a practical technique for...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research