Patterns of age related changes for phosphodiesterase type-10A in comparison with dopamine D 2/3 receptors and sub-cortical volumes in the human basal ganglia: A PET study with 18 F-MNI-659 and 11 C-raclopride with correction for partial volume effect

Neuroimage. 2017 May 15;152:330-339. doi: 10.1016/j.neuroimage.2017.02.047. Epub 2017 Feb 28.

Abstract

Phosphodiesterase 10A enzyme (PDE10A) is an important striatal target that has been shown to be affected in patients with neurodegenerative disorders, particularly Huntington´s disease (HD). PDE10A is expressed on striatal neurones in basal ganglia where other known molecular targets are enriched such as dopamine D2/3 receptors (D2/3 R). The aim of this study was to examine the availability of PDE10A enzyme in relation with age and gender and to compare those changes with those related to D2/3 R and volumes in different regions of the basal ganglia. As a secondary objective we examined the relative distribution of D2/3 R and PDE10A enzyme in the striatum and globus pallidus. Forty control subjects (20F/20M; age: 44±11y, age range 27-69) from an ongoing positron emission tomography (PET) study in HD gene expansion carriers were included. Subjects were examined with PET using the high-resolution research tomograph (HRRT) and with 3T magnetic resonance imaging (MRI). The PDE10A radioligand 18F-MNI-659 and D2/3 R radioligand 11C-raclopride were used. The outcome measure was the binding potential (BPND) estimated with the two-tissue compartment model (18F-MNI-659) and the simplified reference tissue model (11C-raclopride) using the cerebellum as reference region. The PET data were corrected for partial volume effects. In the striatum, PDE10A availability showed a significant age-related decline that was larger compared to the age-related decline of D2/3 R availability and to the age-related decline of volumes measured with MRI. In the globus pallidus, a less pronounced decline of PDE10A availability was observed, whereas D2/3 R availability and volumes seemed to be rather stable with aging. The distribution of the PDE10A enzyme was different from the distribution of D2/3 R, with higher availability in the globus pallidus. These results indicate that aging is associated with a considerable physiological reduction of the availability of PDE10A enzyme in the striatum. Moreover as result of the analysis, in the striatum for both the molecular targets, we observed a gender effect with higher BPND the female group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging*
  • Basal Ganglia / enzymology*
  • Female
  • Humans
  • Image Enhancement
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Phosphoric Diester Hydrolases / metabolism*
  • Phthalimides
  • Positron-Emission Tomography / methods
  • Quinazolinones
  • Raclopride
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*

Substances

  • 2-(2-(3-(4-(2-fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione
  • Phthalimides
  • Quinazolinones
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Raclopride
  • PDE10A protein, human
  • Phosphoric Diester Hydrolases