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Modeling of fluorine-18-6-fluoro-L-Dopa in humans
1Department of Nuclear Medicine, McMaster University Medical Centre Hamilton, Ontario, Canada.
Unlabelled:
Fluorine-18-6-fluoro-L-Dopa (F-Dopa) has been used successfully to evaluate striatal dopaminergic function in humans. The kinetic analysis of F-Dopa studies, however, is confounded by the presence of [18F]6-fluoro-3-O-methyl-L-Dopa (OMFD), the major metabolite of F-Dopa formed in the periphery that crosses the blood-brain barrier. We present results of compartmental analysis in subjects in whom we independently measured the kinetics of OMFD in the blood and striatum, and used this knowledge to solve for the kinetics of F-Dopa.
Methods:
The kinetics of F-Dopa in striatum were measured with PET from 0 to 150 min after an intravenous bolus injection of tracer in four normal subjects and two patients suffering from Parkinson's disease. On a separate occasion, the kinetics of OMFD were determined in the plasma and striatum of the same individuals. The measured OMFD kinetics of each individual allowed us to reduce the number of compartments and rate constants which have to be solved for any compartmental analysis of the kinetics of F-Dopa.
Results:
A two-compartmental, three rate-constant model was sufficient to describe the time course of F-Dopa and its metabolites in the striatum. The rate constant (k21) representing the decarboxylation rate of F-Dopa was 0.0124 min-1 in the normal subjects, and 0.0043 min-1 in the parkinsonian patients.
Conclusion:
The data do not support the need to include a fourth rate constant representing the egress of F-Dopamine and its metabolites. The forward transport rates for F-Dopa and OMFD from plasma to striatum are very similar in humans.