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The Effects of Carbidopa Administration on 6-[¹⁸F]Fluoro-L-DOPA Kinetics in Positron Emission Tomography

John M. Hoffman^*, William P. Melega, Thomas C. Hawk, Scott C. Grafton, Andre Luxen, D. Kirk Mahoney, Jorge R. Barrio, Sung-Cheng Huang, John C. Mazziotta and Michael E. Phelps

Division of Nuclear Medicine and Biophysics, Departments of Radiological Sciences, Pharmacology and Neurology and Laboratory of Nuclear Medicine, Laboratory of Biomedical and Environmental Sciences, UCLA School of Medicine, University of California at Los Angeles, Los Angeles, California

Correspondence: For reprints contact: *John M. Hoffman, Section of Nuclear Medicine, Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710.

ABSTRACT

Carbidopa (L--hydrazino--methyl-b-(3,4-dihydroxyphenyl) propionic acid is a known inhibitor of aromatic amino acid decarboxylase. In both humans and monkeys, we studied the effects of carbidopa on plasma and brain kinetics of 6-[¹⁸F] fluoro-L-DOPA (FDOPA), an analog of L-DOPA used for PET studies of the central dopaminergic system. Pretreatment with carbidopa resulted in increases in the plasma levels of FDOPA and 3-O-methyl-6-[¹⁸F]fluoro-L-DOPA (3-OMFD). Total striatal and cerebellar activities measured with PET were also increased. Furthermore, increases observed in the specific striatal activity (striatum minus cerebellum total activity) were correlated with increases in the plasma FDOPA curve. Carbidopa pretreatment did not affect the influx rate constant (K) for FDOPA from plasma to striatum in humans as determined by Patlak graphical analysis. Thus, an increase in measured striatal tomographic activity was secondary to the increase in plasma FDOPA levels rather than as a result of changes in the FDOPA influx rate constant.

FOOTNOTES

^* Current address: Section of Nuclear Medicine, Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710.

Current address: Cliniques Universitaire, De Bruxelles, Hospital Erasme, Route De Lennik 808, B-1070 Bruxelles, Belgium.

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