A dual-tracer study of extrastriatal 6-[18F]fluoro-m-tyrosine and 6-[18F]-fluoro-L-dopa uptake in Parkinson's disease.
6-[(18)F]-Fluoro-L-dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism--its intense uptake in the striatum, and fainter uptake in other brain regions, is correlated with the symptoms and pathophysiology of Parkinson's disease (PD). 6-[(18)F]fluoro-m-tyrosine (FMT), which also targets L-amino acid decarboxylase, has potential advantages over FDOPA as a radiotracer because it does not form catechol-O-methyltransferase (COMT) metabolites. The purpose of the present study was to compare the regional distribution of these radiotracers in the brains of PD patients. Fifteen Parkinson's patients were studied with FMT and FDOPA positron emission tomography (PET) as well as high-resolution structural magnetic resonance imaging (MRI). MRI's were automatically parcellated into neuroanatomical regions of interest (ROIs) in Freesurfer (http://surfer.nmr.mgh.harvard.edu); region-specific uptake rate constants (Kocc) were generated from coregistered PET using a Patlak graphical approach. The essential findings were as follows: (1) regional Kocc were highly correlated between the radiotracers and in agreement with a previous FDOPA studies that used different ROI selection techniques; (2) FMT Kocc were higher in extrastriatal regions of relatively large uptake such as amygdala, pallidum, brainstem, hippocampus, entorhinal cortex, and thalamus, whereas cortical Kocc were similar between radiotracers; (3) while subcortical uptake of both radiotracers was related to disease duration and severity, cortical uptake was not. These results suggest that FMT may have advantages for examining pathologic changes within allocortical loop structures, which may contribute to cognitive and emotional symptoms of PD.
William S. Middleton Veterans Hospital and Geriatric Research Education and Clinical Center, Madison, Wisconsin; Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Clarence T
CT
Li
Matthew
M
Palotti
James E
JE
Holden
Jen
J
Oh
Ozioma
O
Okonkwo
Bradley T
BT
Christian
Barbara B
BB
Bendlin
Laura
L
Buyan-Dent
Sandra J
SJ
Harding
Charles K
CK
Stone
Onofre T
OT
DeJesus
Robert J
RJ
Nickles
Catherine L
CL
Gallagher
D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007980:Levodopa; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives*
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C080704:6-fluoro-3-tyrosine; C043437:fluorodopa F 18; D014443:Tyrosine; D007980:Levodopa; D004295:Dihydroxyphenylalanine; C015566:3-tyrosine
P.H.S; Parkinson Disease/*physiopathology/*radionuclide imaging; U.S. Gov't; adult; aged; brain mapping; cerebral cortex/metabolism/radionuclide imaging; dihydroxyphenylalanine/*analogs & derivatives/drug effects/pharmacokinetics; dopamine agents/*diagnostic use/pharmacokinetics; humans; research support; tomography; tyrosine/*analogs & derivatives/diagnostic use