title: 6-[18F]fluoro-L-dopa uptake and [76Br]bromolisuride binding in the excitotoxically lesioned caudate-putamen of nonhuman primates studied using positron emission tomography.
abstract: The functional status of the dopaminergic system following striatal excitotoxic lesions was studied in living baboons by positron emission tomography (PET) using 6-[18F]fluoro-L-dopa as specific tracer for the presynaptic dopaminergic terminals and [76Br]bromolisuride as selective dopamine D2-receptor marker. The glutamate receptor agonist ibotenic acid (IA) was injected into the right caudate-putamen of six baboons to induce a neuropathological and behavioral model of Huntington's disease (HD). In vivo PET studies performed 3 to 6 months after the IA injections showed that subtotal excitotoxic lesions of the CP were accompanied by changes in the kinetic of [76Br]bromolisuride binding indicating a dose-dependent reduction in binding sites in the lesioned striatum of all IA-injected animals. In the most severely lesioned animals, there was also a decrease in the uptake of the nigrostriatal dopaminergic marker. The loss of D2-receptors and decrease in striatal dopamine uptake are consistent with clinical and postmortem findings in HD. In addition, the decrease in 6-[18F]fluoro-L-dopa uptake confirms previous studies performed in a rat model of HD suggesting a continuous decline of nigral dopamine cell function following destruction of their intrinsic striatal target neurons. The results of our experience to date in PET studies of 6-[18F]fluoro-L-dopa and [76Br]bromolisuride binding in IA-lesioned primates indicate that PET can identify effects of cell loss on markers of pre- and postsynaptic function in the striatum of living subjects.
authors.affiliation: URA CNRS 1285, Orsay, France.
authors.forename: P
authors.initials: P
authors.lastname: Hantraye
authors.forename: C
authors.initials: C
authors.lastname: Loc'H
authors.forename: B
authors.initials: B
authors.lastname: Maziere
authors.forename: M
authors.initials: M
authors.lastname: Khalili-Varasteh
authors.forename: C
authors.initials: C
authors.lastname: Crouzel
authors.forename: D
authors.initials: D
authors.lastname: Fournier
authors.forename: J C
authors.initials: JC
authors.lastname: Yorke
authors.forename: O
authors.initials: O
authors.lastname: Stulzaft
authors.forename: D
authors.initials: D
authors.lastname: Riche
authors.forename: O
authors.initials: O
authors.lastname: Isacson
mesh_terms: D000818:Animals; D001692:Biological Transport; D001967:Bromine Radioisotopes; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D005462:Fluorine Radioisotopes; D007051:Ibotenic Acid / Q000633:toxicity*; D007700:Kinetics; D008090:Lisuride / Q000031:analogs & derivatives* / Q000378:metabolism; D010215:Papio; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D014055:Tomography, Emission-Computed
chemical_list: D001967:Bromine Radioisotopes; D005462:Fluorine Radioisotopes; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D007051:Ibotenic Acid; C029112:5-fluorodopa; D004295:Dihydroxyphenylalanine; D008090:Lisuride; C039667:bromerguride