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-11C]mirtazapine with a radiochemical-purity >98% in a
21% decay-corrected radiochemical yield by alkylation of N-desmethyl mirtazapine with
[11C]methyl iodide, followed by HPLC purification and formulation. [N-Methyl-11C]mirtazapine
entered the brain readily and, under baseline conditions, it had an apparent volume
of distribution (V(e)') 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-11C]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-11C]mirtazapine from binding sites in the
basal ganglia, thalamus and frontal cortex, but not in reference regions (cerebellum
and olfactory tubercle). Thus, [N-methyl-11C]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.