Session Information
Date: Wednesday, September 25, 2019
Session Title: Neuroimaging
Session Time: 1:15pm-2:45pm
Location: Les Muses Terrace, Level 3
Objective: We aimed to evaluate the role of astroglia activation in Huntington’s disease gene expansion carriers (HDGECs) using [11C]BU99008 PET, a novel radioligand with high specificity and selectivity for imidazoline 2 binding sites (I2BS).
Background: Preclinical studies provide evidence for the critical and pathogenic role of mutant huntingtinin glial cell function suggesting that glial dysfunction may contribute to neuronal cell death in Huntington’s disease (HD). The imidazoline 2 binding sites (I2BS) are expressed on activated astrocytes; by measuring I2BS levels we can indirectly evaluate astrogliosis in HDGECs.
Method: Twelve HDGECs, 5 symptomatic and 7 premanifest HDGECs, and 12 healthy controls (HCs) underwent MRI and [11C]BU9908 PET corrected with arterial input function. Regional volume of distribution (VT) was calculated using the two-tissue compartment model with MIAKAT.
Results: In premanifest HDGECs, increased [11C]BU99008 VT uptake was observed in frontal, temporal, parietal, insular and occipital cortex regions (P<0.05). No differences were observed in the caudate, putamen, thalamus and brainstem. In the group of manifest HDGECs, [11C]BU99008 VT uptake was in line with HCs, showing trends towards decreased binding but not reaching significance. In premanifest HDGECs, increased [11C]BU99008 VT in the anterior (r=0.89; P=0.007) and medial (r=0.79; P=0.036) frontal gyrus, fusiform gyrus (r=0.79; P=0.036), and the insula anterior short (r=0.78; P=0.036) and inferior (r=0.82; P=0.023) cortex correlated with higher probability to symptomatic conversion.
Conclusion: Our findings demonstrate that astrogliosis is an early event in the pathophysiological mechanisms underlying HD and highlights the potential use of [11C]BU99008 PET as a marker to predict symptomatic onset in premanifest HDGECs.
To cite this abstract in AMA style:
H. Wilson, F. Niccolini, G. Dervenoulas, R. Tyacke, J. Myers, R. Gunn, D. Nutt, E. Rabiner, S. Tabrizi, M. Politis. Evaluation of Imidazoline 2 binding sites reflecting astroglia pathology in Huntington’s Disease: An in vivo [11C]BU99008 PET study [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/evaluation-of-imidazoline-2-binding-sites-reflecting-astroglia-pathology-in-huntingtons-disease-an-in-vivo-11cbu99008-pet-study/. Accessed June 3, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluation-of-imidazoline-2-binding-sites-reflecting-astroglia-pathology-in-huntingtons-disease-an-in-vivo-11cbu99008-pet-study/