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RESEARCH PRODUCT

Preliminary in vivo and ex vivo evaluation of the 5-HT2A imaging probe [18F]MH.MZ

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Abstract Introduction The 5-HT 2A receptor is one of the most interesting targets within the serotonergic system because it is involved in a number of important physiological processes and diseases. Methods [ 18 F]MH.MZ, a 5-HT 2A antagonistic receptor ligand, is labeled by 18 F-fluoroalkylation of the corresponding desmethyl analogue MDL 105725 with 2-[ 18 F]fluoroethyltosylate ([ 18 F]FETos). In vitro binding experiments were performed to test selectivity toward a broad spectrum of neuroreceptors by radioligand binding assays. Moreover, first micro-positron emission tomography (μPET) experiments, ex vivo organ biodistribution, blood cell and protein binding and brain metabolism studies of [ 18 F]MH.MZ were carried out in rats. Results [ 18 F]MH.MZ showed a K i of 3 nM toward the 5-HT 2A receptor and no appreciable affinity for a variety of receptors and transporters. Ex vivo biodistribution as well as μPET showed highest brain uptake at ∼5 min p.i. and steady state after ∼30 min p.i. While [ 18 F]MH.MZ undergoes extensive first-pass metabolism which significantly reduces its bioavailability, it is insignificantly metabolized within the brain. The binding potential in the rat frontal cortex is 1.45, whereas the cortex to cerebellum ratio was determined to be 2.7 after ∼30 min. Conclusion Results from μPET measurements of [ 18 F]MH.MZ are in no way inferior to data known for [ 11 C]MDL 100907 at least in rats. [ 18 F]MH.MZ appears to be a highly potent and selective serotonergic PET ligand in small animals.