title: Positron emission tomographic imaging of the dopamine transporter with 11C-WIN 35,428 reveals marked declines in mild Parkinson's disease.
abstract: Parkinson's Disease (PD) is characterized by a selective loss of nigrostriatal dopaminergic neurons that results in a marked reduction of dopaminergic nerve terminals in the striatum. Recently, 11C-WIN 35,428, a cocaine analogue that specifically labels the dopamine transporter, was developed and can be used to label dopaminergic nerve terminals in vivo by positron emission tomography. In healthy control subjects, binding of 11C-WIN 35,428 is highest in the striatum. In addition, 2 symmetrical focal areas of low binding were observed in the midbrain. The cerebellum functioned as an appropriate region for nonspecific binding. The binding of 11C-WIN 35,428 in patients with PD (Hoehn-Yahr II) was compared with that in healthy control subjects by using the (region-cerebellum)/cerebellum ratio for data acquired 34 to 82 minutes after injection. In control subjects, this ratio varied, at approximately 2, in the striatum. In patients with PD, binding in the posterior putamen was reduced by 78%, whereas the anterior putamen and the caudate nucleus showed a reduction of 59 and 39%, respectively. The reduction in 11C-WIN 35,428 binding was highest in the midbrain (84%). The high specific/nonspecific binding ratio and the pronounced reduction in binding in mild PD may permit detection of even earlier stages of PD or presymptomatic individuals with dopaminergic cell loss.
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: J J
authors.initials: JJ
authors.lastname: Frost
authors.forename: A J
authors.initials: AJ
authors.lastname: Rosier
authors.forename: S G
authors.initials: SG
authors.lastname: Reich
authors.forename: J S
authors.initials: JS
authors.lastname: Smith
authors.forename: M D
authors.initials: MD
authors.lastname: Ehlers
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
authors.forename: H T
authors.initials: HT
authors.lastname: Ravert
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000032:analysis* / Q000378:metabolism; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009928:Organ Specificity; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: D015415:Biomarkers; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine