Comparison of [18F]FDOPA, [18F]FMT and [18F]FECNT for imaging dopaminergic neurotransmission in mice.
BACKGROUND
The clinically established positron emission tomography (PET) tracers 6-[(18)F]-fluoro-l-DOPA ([(18)F]FDOPA), 6-[(18)F]-fluoro-l-m-tyrosine ([(18)F]FMT) and 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-[(18)F]-fluoroethyl)-nortropane ([(18)F]FECNT) serve as markers of presynaptic integrity of dopaminergic nerve terminals in humans. This study describes our efforts to adopt the methodology of human Parkinson's disease (PD) PET studies to mice.


METHODS
The PET imaging characteristics of [(18)F]FDOPA, [(18)F]FMT and [(18)F]FECNT were analyzed in healthy C57BL/6 mice using the dedicated small-animal PET tomograph quad-HIDAC. Furthermore, [(18)F]FECNT was tested in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD.


RESULTS
[(18)F]FDOPA and [(18)F]FMT failed to clearly visualize the mouse striatum, whereas PET experiments using [(18)F]FECNT proved that the employed methodology is capable of delineating the striatum in mice with exquisite resolution. Moreover, [(18)F]FECNT PET imaging of healthy and MPTP-lesioned mice demonstrated that the detection and quantification of striatal degeneration in lesioned mice can be accomplished.


CONCLUSIONS
This study shows the feasibility of using [(18)F]FECNT PET to analyze noninvasively the striatal degeneration in the MPTP mouse model of PD. This methodology can be therefore considered as a viable complement to established in vivo microdialysis and postmortem techniques.
Honer
Michael
M
Center for Radiopharmaceutical Science of ETH, PSI and USZ, CH-8093 Zurich, Switzerland. michael.honer@pharma.ethz.ch
Hengerer
Bastian
B
Blagoev
Milen
M
Hintermann
Samuel
S
Waldmeier
Peter
P
Schubiger
Pius A
PA
Ametamey
Simon M
SM
D000818:Animals; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000378:metabolism; D009662:Nortropanes / Q000493:pharmacokinetics*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism*; D009435:Synaptic Transmission; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
C410211:2-carbomethoxy-3-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane; D018377:Neurotransmitter Agents; D009662:Nortropanes; C493093:O-(18F)fluoromethyl-L-tyrosine; D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D004298:Dopamine