The regional distributions of monoamine oxidase (MAO) types A and B have been identified in human brain in vivo with intravenously injected 11C-labeled suicide enzyme inactivators, clorgyline and L-deprenyl, and positron emission tomography. The rapid brain uptake and retention of radioactivity for both 11C tracers indicated irreversible trapping. The anatomical distribution of 11C paralleled the distribution of MAO A and MAO B in human brain in autopsy material. The corpus striatum, thalamus, and brainstem contained high MAO activity. The magnitudes of uptake of both [11C]clorgyline and L-[11C]deprenyl were markedly reduced in one subject treated with the antidepressant MAO inhibitor phenelzine. A comparison of the brain uptake and retention of the 11C-labeled inactive (D-) and active (L-) enantiomers of deprenyl showed rapid clearance of the inactive enantiomer and retention of the active enantiomer within MAO B-rich brain structures, in agreement with the known stereoselectivity of MAO B for L-deprenyl. Prior treatment with unlabeled L-deprenyl prevented retention of L-[11C]deprenyl. Thus, suicide enzyme inactivators labeled with positron emitters can be used to quantitate the distribution and kinetic characteristics of MAO in human brain structures.

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By use of Positron Emission Tomography (PET), dynamic studies of the metabolism within the feto-maternal unit can be performed using various tracers. Many compounds like amino acids, carbohydrates, fatty acids and drugs can be performed using various tracers. Many compounds like amino acids, carbohydrates, fatty acids and drugs can be labelled with 11C and used as tracers. 11C-labelled L- or D-methionine was injected intravenously into pregnant Rhesus monkeys. The distribution of the radioactivity in maternal muscles, aorta, placenta and the liver of the fetus was quantitatively estimated as a function of time. Simultaneously blood, urine and amniotic fluid samples were analyzed for 11C-activity. The distribution of 11C between the high and the low molecular fraction of plasma (MW greater than 5000) was studied after gel filtration. Both when 11C-L- and D-methionine were given, the radioactivity rapidly crossed the placenta and was accumulated in the fetal liver. In the 11C-L-methionine experiments, about 70 per cent of the radioactivity in plasma was found in the high molecular fraction one hour after injection. A greater part of 11C-D-compared to 11C-L-activity was excreted in the urine.

11C-labelled L-deprenyl in vitro autoradiography was used to study the regional distribution of MAO-B in human brain. 80 microns thick cryosections from two human brains, a 67 years old female and a 58 years old male, were taken on tape/paper and transferred on to a gelatinized glass plate. The sections were then incubated with 34 and 54 nM 11C-L-deprenyl for 15 min and exposed to a film sensitive to high energy radiation for 2 hours. The autoradiograms obtained were analyzed by computerized densiotometry. High 11C-deprenyl binding was found in the caudate nucleus, putamen, thalamus, substantia nigra, medial and lateral geniculate bodies, hippocampus and periaqueductal gray. Moderate to low binding was observed in cerebral cortex. Cerebral cortex and white matter showed the lowest binding. The autoradiographic technique described proved to be a fast and reliable method to investigate the topographic localization of MAO-B in large cryosections of human brain.