Detection of monoamine oxidase a in brain of living rats with [18F]fluoroethyl-harmol PET

Monoamine oxidase A (MAO-A) in brain, sympathetic fibres, and neuroendocrine tissues can catalyze the oxidative deamination of serotonin, noradrenaline and adrenaline, and contributes, along with MAO-B,to the catabolism of brain dopamine. As such, MAO-A is potentially an important target for molecular imaging, although the repertoire of suitable radiotracers is rather limited. The first successful MAO-A ligand for positron emission tomography (PET) studies of MAO-A was the b-carboline [11 C]harmine, which binds reversibly with nM affinity and high selectivity to the enzyme (Bergstrom et al., 1997). In contrast, the cerebral binding to MAO-A of [11C]clorgyline is difficult to quantify since the rate constant for irreversible binding is so very high, and due to the presence of a nonspecific binding component in white matter (Fowler et al., 2001). Other reversibly binding PET ligands for MAO-A include [11 C]befloxatone (Zanotti-Fregonara et al., 2013) and [11 C]befloxatone (Zanotti-Fregonara et al., 2013) and [11 CROMAO (Jensen et al., 2008). However, only [11 C]harmine is currently finding use in human PET studies of brain MAO-A (Chiuccariello et al., 2014). Logistic issues arising from the brief half-life of carbon-11 may be limiting the wider use of [11 C]harmine and other MAO-A ligands in research. Obtaining an MAO-A ligand labelled with fluorine-18 might afford multiple scans from a single radiosynthesis, and would make MAO-A scanning available to research centers lacking a medical cyclotron. In two preliminary reports, the b- carboline [18 F]fluoroethyl-harmol was found to have good properties for imaging in vivo, including high affinity and specificity, while corresponding PEGylated derivatives did not cross the blood-brain-barrier (Blom et al., 2008; Schieferstein et al., 2012). However, the specific binding of [18 F]fluoroethyl-harmol was not reported in detail in those reports. In this study, we report a high yield radiosynthesis of [18 F]fluoroethyl- harmol, and use small animal PET to map the distribution of its specific binding in brain of living rat