[11C]Mirtazapine for PET neuroimaging:: radiosynthesis and initial evaluation in the living porcine brain

We radiolabelled mirtazapine, a tetracyclic, atypical, antidepressant drug, for positron emission tomography (PET) and evaluated its regional kinetics in the living porcine brain. We produced [N-methyl-C-11]mirtazapine with a radiochemical-purity >98% in a 21% decay-corrected radiochemical yield by alkylation of N-desmethyl mirtazapine with [C-11]methyl iodide, followed by HPLC purification and formulation. [N-Methyl-C-11]mirtazapine entered the brain readily and, under baseline conditions, it had an apparent volume of distribution (V-c(i)) of 9-13 in the basal ganglia, thalamus, and frontal cortex. Reference region and graphical analyses based on a one-compartment model showed that the binding of [N-methyl-C-11]mirtazapine was reversible, with an apparent binding potential of more than two in thalamus and frontal cortex. Infusion of unlabelled mirtazapine markedly displaced [N-methyl-C-11]mirtazapine from binding sites in the basal ganglia, thalamus and frontal cortex, but not in reference regions (cerebellum and olfactory tubercle). Thus, [N-methyl-C-11]mirtazapine showed rapid passage into the living brain, slow metabolism in blood, and reversible, competitive binding, which may make it useful for PET neuroimaging of neuroreceptors involved in antidepressant actions. (C) 2002 Elsevier Science B.V./ECNP. All rights reserved.