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

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 [C-11]clorgyline and deuterium-substituted [C-11]clorgyline ([C-11]clorgyline-D2) to better understand the molecular link between [C-11]clorgyline binding and MAO A. In PET studies of five normal healthy volunteers scanned with [C-11]clorgyline and [C-11]clorgyline-D2 2 h apart, deuterium substitution generally produced the expected reductions in the brain uptake of [C-11]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 [C-11]clorgyline-D2. Thus deuterium-substituted [C-11]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.