title: Change in PDE10 across early Huntington disease assessed by [18F]MNI-659 and PET imaging.
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).
  
  
  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.
  
  
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT. drussell@indd.org.
authors.forename: David S
authors.initials: DS
authors.lastname: Russell
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT.
authors.forename: Danna L
authors.initials: DL
authors.lastname: Jennings
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT.
authors.forename: Olivier
authors.initials: O
authors.lastname: Barret
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT.
authors.forename: Gilles D
authors.initials: GD
authors.lastname: Tamagnan
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Carroll
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT.
authors.forename: Fabien
authors.initials: F
authors.lastname: Caillé
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT.
authors.forename: David
authors.initials: D
authors.lastname: Alagille
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Morley
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT.
authors.forename: Caroline
authors.initials: C
authors.lastname: Papin
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT.
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.affiliation: From the Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, CT.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Marek
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism*; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010797:Phthalimides / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000639:trends*; D052999:Quinazolinones / Q000378:metabolism*
chemical_list: C000599323:2-(2-(3-(4-(2-fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione; D015415:Biomarkers; D005462:Fluorine Radioisotopes; D010797:Phthalimides; D052999:Quinazolinones; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases