title: Effect of dopamine loss and the metabolite 3-O-methyl-[18F]fluoro-dopa on the relation between the 18F-fluorodopa tissue input uptake rate constant Kocc and the [18F]fluorodopa plasma input uptake rate constant Ki.
abstract: Parkinson disease is characterized by the loss of dopaminergic neurons, thus decreasing the system's ability to produce and store dopamine (DA). Such ability is often investigated using 18F-fluorodopa (FD) positron emission tomography. A commonly used model to investigate the DA synthesis and storage rate is the modified Patlak graphical approach. This approach allows for both plasma and tissue input functions, yielding the respective uptake rate constants K(i) and K(occ). This method requires the presence of an irreversible compartment and the absence of any nontrapped tracer metabolite. In the case of K(occ), this last assumption is violated by the presence of the FD metabolite 3-O-methyl-[18F]fluoro-dopa (3OMFD), which makes the K(occ) evaluation susceptible to a downward bias. It was found that both K(i) and K(occ) are influenced by DA loss and thus are not pure measures of DA synthesis and storage. In the case of K(occ), the presence of 3OMFD exacerbates the effect of DA egress, thus introducing a disease-dependent bias in the K(occ) determination. These findings imply that K(i) and K(occ) provide different assessments of disease severity and that, as disease progresses, K(i) and especially K(occ) become more related to DA storage capacity and less to the DA synthesis rate.
authors.affiliation: Pacific Parkinson's Research Centre, Room M37, Purdy Pavilion, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5. vesna@triumf.ca
authors.forename: V
authors.initials: V
authors.lastname: Sossi
authors.forename: J E
authors.initials: JE
authors.lastname: Holden
authors.forename: R
authors.initials: R
authors.lastname: de la Fuente-Fernandez
authors.forename: T J
authors.initials: TJ
authors.lastname: Ruth
authors.forename: A J
authors.initials: AJ
authors.lastname: Stoessl
mesh_terms: D000328:Adult; D000368:Aged; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D012016:Reference Values; D012720:Severity of Illness Index
chemical_list: D005462:Fluorine Radioisotopes; C055151:3-O-methyl-6-fluoro-dopa; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine