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\ud 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,\ud 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\ud matter (Fowler et al., 2001). Other reversibly binding\ud PET ligands for MAO-A include [11 C]befloxatone (Zanotti-Fregonara et al., 2013) and [11 C]ROMAO (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\ud ligand labelled with fluorine-18 might afford multiple\ud scans from a single radiosynthesis, and would make\ud MAO-A scanning available to research centers lacking\ud a medical cyclotron. In two preliminary reports, the b-\ud carboline [18 F]fluoroethyl-harmol was found to have\ud good properties for imaging in vivo, including high\ud affinity and specificity, while corresponding PEGylated\ud derivatives did not cross the blood-brain-barrier (Blom\ud et al., 2008; Schieferstein et al., 2012). However, the\ud specific binding of [18 F]fluoroethyl-harmol was not\ud reported in detail in those reports. In this study, we\ud report a high yield radiosynthesis of [18 F]fluoroethyl-\ud harmol, and use small animal PET to map the distribution of its specific binding in brain of living rat