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Change in PDE10 across early Huntington disease assessed by [18F]MNI-659 and PET imaging.
- Source :
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Neurology [Neurology] 2016 Feb 23; Vol. 86 (8), pp. 748-54. Date of Electronic Publication: 2016 Jan 22. - Publication Year :
- 2016
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Abstract
- Objective: To evaluate whether striatal [(18)F]MNI-659 PET imaging of phosphodiesterase 10A (PDE10) serves as a sensitive and reliable biomarker of striatal neurodegeneration in a longitudinal cohort of participants with early Huntington disease (HD).<br />Methods: A cohort of participants with HD, including both participants premanifest or manifest with motor signs, underwent clinical assessments, genetic determination, and 2 [(18)F]MNI-659 PET imaging sessions approximately 1 year apart. Eleven healthy control (HC) participants underwent clinical assessments and [(18)F]MNI-659 PET imaging once. Striatal binding potentials (BPnd) were estimated for brain regions of interest, specifically within the basal ganglia, and compared between baseline and follow-up imaging. Clinical measures of HD severity were assessed at each visit.<br />Results: Eight participants with HD (6 manifest; 2 premanifest) participated. Of those with manifest HD, all had relatively early stage disease (stage 1, n = 2; stage 2, n = 4) and a Unified Huntington's Disease Rating Scale total motor score <45. As expected, the HD cohort as a whole had a reduction in the basal ganglia BPnd to approximately 50% of that seen in HC. On follow-up scans, [(18)F]MNI-659 uptake declined in the putamen and caudate nucleus in all 8 participants. The mean annualized rates of decline in signal in the caudate, putamen, and globus pallidus and the putamen were 16.6%, 6.9%, and 5.8%, respectively. In HC, the annualized reduction in signal in striatal regions was less than 1%.<br />Conclusion: Longitudinal data in this small cohort of participants with early HD support [(18)F]MNI-659 PET imaging of PDE10 as a useful biomarker to track HD disease progression.<br /> (© 2016 American Academy of Neurology.)
- Subjects :
- Adult
Aged
Biomarkers metabolism
Cohort Studies
Disease Progression
Female
Humans
Longitudinal Studies
Male
Middle Aged
Fluorine Radioisotopes metabolism
Huntington Disease diagnostic imaging
Huntington Disease metabolism
Phosphoric Diester Hydrolases metabolism
Phthalimides metabolism
Positron-Emission Tomography trends
Quinazolinones metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1526-632X
- Volume :
- 86
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Neurology
- Publication Type :
- Academic Journal
- Accession number :
- 26802091
- Full Text :
- https://doi.org/10.1212/WNL.0000000000002391