Selective reduction of radiotracer trapping by deuterium substitution: comparison of carbon-11-L-deprenyl and carbon-11-deprenyl-D2 for MAO B mapping.

UNLABELLED: Recent human PET studies with the monoamine oxidase B (MAO B) tracer [11C]L-deprenyl show that the rapid rate of radiotracer trapping relative to transport reduces the sensitivity of the tracer in regions of high MAO B concentration. This study investigates the use of deuterium substituted L-deprenyl ([11C]L-deprenyl-D2) to reduce the rate of trapping in tissue and to improve sensitivity.
METHODS: Five normal subjects (43-64 yr) were studied with [11C]L-deprenyl and [11C]L-deprenyl-D2 on the same day. Time-activity data from different brain regions and the arterial plasma were analyzed using a three-compartment model as well as graphical analysis for irreversible systems.
RESULTS: For both tracers, maximum radioactivity accumulation occurred at about 5 min. For [11C]L-deprenyl, 11C concentration peaked at 5 min and remained constant throughout the study. With [11C]L-deprenyl-D2, peak 11C concentration also occurred at about 5 min but was followed by an initial washout. Carbon-11 concentration generally plateaued from 30 to 60 min. The plateau for [11C]L-deprenyl was higher than the plateau for [11C]L-deprenyl-D2. Data analysis by a three-compartment model and by graphical analysis showed that deuterium substitution: (a) does not affect plasma to tissue transport (K1); (b) reduces the rate of trapping of 11C in all brain regions; (c) facilitates the separation of model terms related to radiotracer delivery from radiotracer trapping in tissue; and (d) improves tracer sensitivity.
CONCLUSION: This study demonstrates that deuterium substitution causes a significant reduction in the rate of trapping of labeled deprenyl, providing a direct link between radiotracer uptake and MAO B in the human brain and enhancing tracer sensitivity to changes in MAO B concentration.