Distribution and kinetics of 3-O-methyl-6-[18F]fluoro-L-dopa in the rhesus monkey brain.
Most attempts to model accurately [18F]-DOPA imaging of the dopamine system are based on the assumptions that its main peripheral metabolite, 3-O-methyl-6-[18F]fluoro-L-DOPA ([18F]3-OM-DOPA), crosses the blood-brain barrier but is present as a homogenous distribution throughout the brain, in part because it is not converted into [18F]DOPA in significant quantities. These assumptions were based mainly on data in rodents. Little information is available in the primate. To verify the accuracy of the above assumptions, we administered 18F-labeled 3-OM-DOPA to normal rhesus monkeys and animals with lesions of the DA nigrostriatal system. No selective 18F regional accumulation in brain was apparent in normal or lesioned animals. The plasma metabolite analysis revealed that only the negatively charged metabolites (e.g., sulfated conjugates) that do not cross the blood-brain barrier were found in significant quantities in the plasma. A one-compartment, three-parameter model was adequate to describe the kinetics of [18F]3-OM-DOPA. In conclusion, assumptions concerning [18F]3-OM-DOPA's behavior in brain appear acceptable for [18F]DOPA modeling purposes.
Doudet
D J
DJ
Section on Clinical Brain Imaging, LCM, NIMH, IRP, Bethesda, Maryland.
McLellan
C A
CA
Carson
R
R
Adams
H R
HR
Miyake
H
H
Aigner
T G
TG
Finn
R T
RT
Cohen
R M
RM
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D008253:Macaca mulatta; D011877:Radionuclide Imaging; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D005462:Fluorine Radioisotopes; D014443:Tyrosine; C008404:3-methoxytyrosine