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 [ 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.