Delayed L-phenylalanine infusion allows for simultaneous kinetic analysis and improved evaluation of specific-to-nonspecific fluorine-18-dopa uptake in brain.
The accumulation of 3-O-methyl-6-[18F]fluoro-L-DOPA (18F-30M-DOPA) in the brain from the circulation is responsible for most of the nonspecific background during 18F-DOPA positron emission tomography scanning. To increase the sensitivity of 18F-DOPA for imaging presynaptic dopamine systems, we took advantage of 18F-30M-DOPA's rapid clearance from the brain (T1/2 approximately 15-20 min). The infusion of the unlabeled amino acid L-phenylalanine, starting 75 min after 18F-DOPA administration, prevents 18F-30M-DOPA entrance into the brain through competition at the large amino acid transport system of the blood brain barrier. This method produces high specific-to-nonspecific contrast images of 18F accumulation beginning 15-30 min after onset of amino acid infusion and better sensitivity to small changes in 18F-DOPA uptake while still allowing for kinetic analysis of the data in the early time points. Kinetic and anatomical data were found to be strongly correlated.
Doudet
D J
DJ
Section on Clinical Brain Imaging, LCM, NIMH, IRP Bethesda, Maryland.
McLellan
C A
CA
Aigner
T G
TG
Wyatt
R J
RJ
Cohen
R M
RM
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D002230:Carbidopa / Q000494:pharmacology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D020267:MPTP Poisoning; D008253:Macaca mulatta; D010649:Phenylalanine / Q000008:administration & dosage*; D013997:Time Factors; D014055:Tomography, Emission-Computed
C055151:3-O-methyl-6-fluoro-dopa; C043437:fluorodopa F 18; D010649:Phenylalanine; D004295:Dihydroxyphenylalanine; D002230:Carbidopa