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


CONCLUSIONS
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.
Fowler
J S
JS
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973-5000, USA.
Wang
G J
GJ
Logan
J
J
Xie
S
S
Volkow
N D
ND
MacGregor
R R
RR
Schlyer
D J
DJ
Pappas
N
N
Alexoff
D L
DL
Patlak
C
C
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology*; D002250:Carbon Radioisotopes; D003903:Deuterium; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000032:analysis*; D012642:Selegiline; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D012642:Selegiline; D003903:Deuterium; D008995:Monoamine Oxidase