Synthesis and evaluation of a targeted PET radioligand [18F]FCOB02 for monoamine oxidase B

Abstract

Monoamine oxidase B (MAO-B) is a membrane-bound flavinase that plays an important role in the regulation of monoamine neurotransmission. Positron emission tomography (PET) provides a way to study the molecular mechanisms of MAO-B-related diseases and to evaluate the effects of drugs. In this study, we designed and synthesized [¹⁸F]FCOB02, a 4-methylcoumarin-like targeting probe.[¹⁸F]FCOB02 is straightforward to synthesize and has a high affinity for MAO-B with an IC₅₀ = 10.68 ± 3.25 nM. Successful radiolabeling with fluorine-18 was achieved, resulting in a labeling rate of 35 % along with favorable lipid solubility (log D_7.4 = 2.4). Automated radiolabelling was achieved after optimization of the conditions. The radiochemical yield was 9.6 % ± 1.2 %(n = 3) with good radiochemical purity (>98 %), good stability in saline for 4 h and high specific activity (105.08 ± 19GBq/μmol，n = 3). Biodistribution studies conducted in mice revealed significant initial brain uptake of 8.22 ± 0.86 % ID/g at 2 min post-injection, followed by rapid metabolism primarily via the liver and kidneys. Brain uptake was comparable to the same type of probe [¹⁸F]SMBT-1 (brain _2min = 7.85 % ID/g). PET-CT images of [¹⁸F]FCOB02 in SD rats showed significant differences in brain uptake before and after inhibition by the inhibitor L-deprenyl. Whole brain uptake was reduced by 20 % after inhibition, indicating specific uptake of the probe in the brain, with a 40-min brain clearance rate of 81 %. The potential utility of [¹⁸F]FCOB02 for achieving specific MAO-B imaging as well as quantitative analysis in vivo warrants further investigation regarding its clinical translational value.