Selective reduction of radiotracer trapping by deuterium substitution: Comparison of carbon-11-L-deprenyl and carbon-11-deprenyl-D2 for MAO B mapping
- Brookhaven National Lab., Upton, NY (United States)
Recent human PET studies with the monoamine oxidase B (MAO B) tracer [{sup 11}C]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 dueterium substituted L-deprenyl ([{sup 11}C]L-deprenyl-D2) to reduce the rate of trapping in tissue and to improve sensitivity. Five normal subjects (43-64 yr) were studied with [{sup 11}C]L-deprenyl and [{sup 11}C]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. For both tracers, maximum radioactivity accumulation occurred at about 5 min. For [{sup 11}C]-deprenyl, {sup 11}C concentration peaked at 5 min and remained constant throughout the study. With [{sup 11}C]L-deprenyl-D2, peak {sup 11}C 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 [{sup 11}C]L-deprenyl was higher than the plateau for [{sup 11}C]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 (K{sub 1}); (b) reduces the rate of trapping of {sup 11}C 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. 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. 38 refs., 8 figs., 2 tabs.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- DOE Contract Number:
- AC02-76CH00016
- OSTI ID:
- 258955
- Journal Information:
- Journal of Nuclear Medicine, Vol. 36, Issue 7; Other Information: PBD: Jul 1995
- Country of Publication:
- United States
- Language:
- English
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