title: In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease.
abstract: Clinical symptoms of Parkinson's disease (PD) do not manifest until dopamine (DA) neuronal loss reaches a symptomatic threshold. To explore the mechanisms of functional compensation that occur in presynaptic DA nerve terminals in PD, we compared striatal positron emission tomographic (PET) measurements by using [11C]dihydrotetrabenazine ([11C]DTBZ; labeling the vesicular monoamine transporter type 2), [11C]methylphenidate (labeling the plasma membrane DA transporter), and [18F]dopa (reflecting synthesis and storage of DA). Three consecutive PET scans were performed in three-dimensional mode by using each tracer on 35 patients and 16 age-matched, normal controls. PET measurements by the three tracers were compared between subgroups of earlier and later stages of PD, between drug-naive and drug-treated subgroups of PD, and between subregions of the parkinsonian striatum. The quantitative relationships of [18F]dopa and [11]DTBZ, and of [11C]methylphenidate and [11C]DTBZ, were compared between the PD and the normal control subjects. We found that [18F]dopa Ki was reduced less than the binding potential (Bmax/Kd) for [11C]DTBZ in the parkinsonian striatum, whereas the [11C]methylphenidate binding potential was reduced more than [11C]DTBZ binding potential. These observations suggest that the activity of aromatic L-amino acid decarboxylase is up-regulated, whereas the plasma membrane DA transporter is down-regulated in the striatum of patients with PD.
authors.affiliation: Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, British Columbia, Canada.
authors.forename: C S
authors.initials: CS
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Samii
authors.forename: V
authors.initials: V
authors.lastname: Sossi
authors.forename: T J
authors.initials: TJ
authors.lastname: Ruth
authors.forename: M
authors.initials: M
authors.lastname: Schulzer
authors.forename: J E
authors.initials: JE
authors.lastname: Holden
authors.forename: J
authors.initials: J
authors.lastname: Wudel
authors.forename: P K
authors.initials: PK
authors.lastname: Pal
authors.forename: R
authors.initials: R
authors.lastname: de la Fuente-Fernandez
authors.forename: D B
authors.initials: DB
authors.lastname: Calne
authors.forename: A J
authors.initials: AJ
authors.lastname: Stoessl
mesh_terms: D000368:Aged; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D015536:Down-Regulation / Q000502:physiology; D005462:Fluorine Radioisotopes; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D013747:Tetrabenazine / Q000031:analogs & derivatives; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C032811:dihydrotetrabenazine; D004298:Dopamine; D006719:Homovanillic Acid; D013747:Tetrabenazine