Anatomic and biochemical correlates of the dopamine transporter ligand 11C-PE2I in normal and parkinsonian primates: comparison with 6-[18F]fluoro-L-dopa.
Positron emission tomography (PET) coupled to 6-[18F]Fluoro-L-Dopa (18F-Dopa) remains the gold standard for assessing dysfunctionality concerning the dopaminergic nigrostriatal pathway in Parkinson's disease and related disorders. The use of ligands of the dopamine transporters (DAT) is an attractive alternative target; consequently, the current aim was to validate one of them, 11C-PE2I, using a multiinjection modeling approach allowing accurate quantitation of DAT densities in the striatum. Experiments were performed in three controls, three MPTP-treated (parkinsonian) baboons, and one reserpine-treated baboon. 11C-PE2I B'max values obtained with this approach were compared with 18F-Dopa input rate constant values (Ki), in vitro Bmax binding of 125I-PE2I, and the number of dopaminergic neurons in the substantia nigra estimated postmortem by stereology. In the caudate nucleus and putamen, control values for 11C-PE2I B'max were 673 and 658 pmol/mL, respectively, whereas it was strongly reduced in the MPTP-treated (B'max = 26 and 36 pmol/mL) and reserpine-treated animals (B'max = 338 and 483 pmol/mL). In vivo 11C-PE2I B'max values correlated with 18F-Dopa Ki values and in vitro 125I-PE2I Bmax values in the striatum and with the number of nigral dopaminergic neurons. Altogether, these data support the use of 11C-PE2I for monitoring striatal dopaminergic disorders and the effect of potential neuroprotective strategies.
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URA CEA CNRS 2210 and Service Hospitalier Frédéric Joliot, Département de Recherche Médicale, Direction des Sciences du Vivant, CEA, Orsay Cedex, France.
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Grégoire
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Frouin
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Coulon
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Fuseau
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Hinnen
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Hantraye
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Bottlaender
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000032:analysis* / Q000378:metabolism; D002421:Caudate Nucleus / Q000737:chemistry / Q000378:metabolism; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism; D003342:Corpus Striatum / Q000737:chemistry; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D007700:Kinetics; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009662:Nortropanes / Q000378:metabolism*; D010215:Papio; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011699:Putamen / Q000737:chemistry / Q000378:metabolism; D012110:Reserpine / Q000008:administration & dosage; D013378:Substantia Nigra / Q000737:chemistry / Q000378:metabolism; D014055:Tomography, Emission-Computed; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009419:Nerve Tissue Proteins; D009662:Nortropanes; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D012110:Reserpine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase