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Validation of midbrain positron emission tomography measures for nigrostriatal neurons in macaques.
- Source :
-
Annals of neurology [Ann Neurol] 2013 Oct; Vol. 74 (4), pp. 602-10. Date of Electronic Publication: 2013 Sep 16. - Publication Year :
- 2013
-
Abstract
- Objective: Development of an effective therapy to slow the inexorable progression of Parkinson disease requires a reliable, objective measurement of disease severity. In the present study, we compare presynaptic positron emission tomography (PET) tracer uptake in the substantia nigra (SN) to cell loss and motor impairment in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primates.<br />Methods: Presynaptic PET tracers 6-[(18)F]-fluorodopa (FD), [(11)C]-2β-methoxy-3β-4-fluorophenyltropane (CFT), and [(11)C]-dihydrotetrabenazine (DTBZ) were used to measure specific uptake in the SN and striatum before and after a variable dose of MPTP in nonhuman primates. These in vivo PET-based measures were compared with motor impairment, as well as postmortem tyrosine hydroxylase-positive cell counts and striatal dopamine concentration.<br />Results: We found the specific uptake of both CFT and DTBZ in the SN had a strong, significant correlation with dopaminergic cell counts in the SN (R(2) = 0.77, 0.53, respectively, p < 0.001), but uptake of FD did not. Additionally, both CFT and DTBZ specific uptake in the SN had a linear relationship with motor impairment (rs = -0.77, -0.71, respectively, p < 0.001), but FD uptake did not.<br />Interpretation: Our findings demonstrate that PET-measured binding potentials for CFT and DTBZ for a midbrain volume of interest targeted at the SN provide faithful correlates of nigral neuronal counts across a full range of lesion severity. Because these measures correlate with both nigral cell counts and parkinsonian ratings, we suggest that these SN PET measures are relevant biomarkers of nigrostriatal function.<br /> (© 2013 American Neurological Association.)
- Subjects :
- Animals
Carbon Isotopes
Disease Models, Animal
Fluorodeoxyglucose F18
MPTP Poisoning diagnostic imaging
Macaca mulatta
Magnetic Resonance Imaging
Male
Substantia Nigra diagnostic imaging
Tetrabenazine analogs & derivatives
MPTP Poisoning pathology
Mesencephalon pathology
Neurons physiology
Positron-Emission Tomography
Substantia Nigra pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1531-8249
- Volume :
- 74
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Annals of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 23686841
- Full Text :
- https://doi.org/10.1002/ana.23939