Objective: The present research describes a new radiosynthesis of 5-(4-((4-[18F]fluorobenzyl)oxy)-3-methoxybenzyl)pyrimidine- 2,4-diamine as a potential radioligand for colony-stimulating factor 1 receptor (CSF-1R) and tyrosine kinase B/C (TrkB/C) neuroreceptors.
Methods: Radiofluorination of a boronic acid precursor followed by thermal deprotection of Boc-protecting groups avoided acidcatalyzed protodeboronation in 8.7 ± 2.8% radiochemical yield.
Results: Competitive autoradiographic binding research indicated a high unspecific binding, and that binding to TrkB/C could be blocked while binding to CSF-1R was not. In a rat model, a positron emission tomography (PET) scan indicated a moderate brain uptake and slow clearance rate.
Conclusion: Moreover, the poor pharmacokinetic features of 5-(4-((4-[18F]fluorobenzyl)oxy)-3-methoxybenzyl)pyrimidine-2,4- diamine prevented its utilization as a PET radioligand in brain scanning, but 1-pot synthesis (which is a strategy to improve the effectiveness of the chemical reaction occurring by the use of copper, 18F-fluorination, and Boc deprotection) is an approach to the radio-synthesis of PET tracers (which are sensitive to acid).
Key words: Tyrosine kinase; Colony-stimulating factor 1 receptor; 18F; Positron emission tomography
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