Distribution of cholinergic nerve terminals in the aged human brain measured with [18F]FEOBV PET and its correlation with histological data
Niels Okkels,
Jacob Horsager,
Miguel A. Labrador-Espinosa,
Frederik O. Hansen,
Katrine B. Andersen,
Mie Kristine Just,
Tatyana D. Fedorova,
Casper Skjærbæk,
Ole L. Munk,
Kim V. Hansen,
Hanne Gottrup,
Allan K. Hansen,
Michel J. Grothe,
Per Borghammer
Affiliations
Niels Okkels
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; Corresponding author at: Department of Nuclear Medicine and PET, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, J220, Aarhus N 8200, Denmark
Jacob Horsager
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark
Miguel A. Labrador-Espinosa
Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
Frederik O. Hansen
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Katrine B. Andersen
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Mie Kristine Just
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Tatyana D. Fedorova
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Casper Skjærbæk
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Ole L. Munk
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Kim V. Hansen
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark
Hanne Gottrup
Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
Allan K. Hansen
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Nuclear Medicine, Aalborg University Hospital, Aalborg, Denmark
Michel J. Grothe
Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
Per Borghammer
Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark
Introduction: [18F]fluoroetoxybenzovesamicol ([18F]FEOBV) is a positron emission topography (PET) tracer for the vesicular acetylcholine transporter (VAChT), a protein located predominantly in synaptic vesicles in cholinergic nerve terminals. We aimed to use [18F]FEOBV PET to study the cholinergic topography of the healthy human brain. Materials and methods: [18F]FEOBV PET brain data volumes of healthy elderly humans were normalized to standard space and intensity-normalized to the white matter. Stereotactic atlases of regions of interest were superimposed to describe and quantify tracer distribution. The spatial distribution of [18F]FEOBV PET uptake was compared with histological and gene expression data. Results: Twenty participants of both sexes and a mean age of 73.9 ± 6.0 years, age-range [64; 86], were recruited. Highest tracer binding was present in the striatum, some thalamic nuclei, and the basal forebrain. Intermediate binding was found in most nuclei of the brainstem, thalamus, and hypothalamus; the vermis and flocculonodular lobe; and the hippocampus, amygdala, insula, cingulate, olfactory cortex, and Heschl's gyrus. Lowest binding was present in most areas of the cerebral cortex, and in the cerebellar nuclei and hemispheres. The spatial distribution of tracer correlated with immunohistochemical post-mortem data, as well as with regional expression levels of SLC18A3, the VAChT coding gene. Discussion: Our in vivo findings confirm the regional cholinergic distribution in specific brain structures as described post-mortem. A positive spatial correlation between tracer distribution and regional gene expression levels further corroborates [18F]FEOBV PET as a validated tool for in vivo cholinergic imaging. The study represents an advancement in the continued efforts to delineate the spatial topography of the human cholinergic system in vivo.
