Non‐MAO A binding of clorgyline in white matter in human brain

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Abstract
Clorgyline is an irreversible inhibitor of monoamine oxidase (MAO A) which has been labeled with carbon‐11 (C‐11) and used to measure human brain MAO A with positron emission tomography (PET). In this study we compared [11C]clorgyline and deuterium‐substituted [11C]clorgyline ([11C]clorgyline‐D2) to better understand the molecular link between [11C]clorgyline binding and MAO A. In PET studies of five normal healthy volunteers scanned with [11C]clorgyline and [11C]clorgyline‐D2 2 h apart, deuterium substitution generally produced the expected reductions in the brain uptake of [11C]clorgyline. However, the reduction was not uniform with the C‐11 binding in white matter being significantly less sensitive to deuterium substitution than other brain regions. The percentages of the total binding attributable to MAO A is largest for the thalamus and smallest for the white matter and this is clearly seen in PET images with [11C]clorgyline‐D2. Thus deuterium‐substituted [11C]clorgyline selectively reduces the MAO A binding component of clorgyline in the human brain revealing non‐MAO A binding which is most apparent in the white matter. The characterization of the non‐MAO A binding component of this widely used MAO A inhibitor merits further investigation.