title: Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands.
abstract: In the quantification of positron emission tomography (PET) radiotracer binding, a commonly used method is reference tissue modeling (RTM). RTM necessitates a proper reference and a ubiquitous choice for G-protein coupled receptors is the cerebellum. We investigated regional differences in uptake within the grey matter of the cerebellar hemispheres (CH), the cerebellar white matter (CW), and the cerebellar vermis (CV) for five PET radioligands targeting the serotonin system. Furthermore, we evaluated the impact of choosing different reference regions when quantifying neocortical binding. The PET and MR images are part of the Cimbi database: 5-HT1AR ([11C]CUMI-101, n = 8), 5-HT1BR ([11C]AZ10419369, n = 36), 5-HT2AR ([11C]Cimbi-36, n = 29), 5-HT4R ([11C]SB207145, n = 59), and 5-HTT ([11C]DASB, n = 100). We employed SUIT and FreeSurfer to delineate CV, CW, and CH and quantified mean standardized uptake values (SUV) and nondisplaceable neocortical binding potential (BPND). Statistical difference was assessed with paired nonparametric two-sided Wilcoxon signed-rank tests and multiple comparison corrected via false discovery rate. We demonstrate significant radioligand specific regional differences in cerebellar uptake. These differences persist when using different cerebellar regions for RTM, but the influence on the neocortical BPNDis small. Nevertheless, our data highlight the importance of validating each radioligand carefully for defining the optimal reference region.
authors.affiliation: 1 Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ganz
authors.affiliation: 1 Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ling
authors.initials: L
authors.lastname: Feng
authors.affiliation: 1 Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hanne Demant
authors.initials: HD
authors.lastname: Hansen
authors.affiliation: 1 Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark.|2 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Vincent
authors.initials: V
authors.lastname: Beliveau
authors.affiliation: 1 Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.affiliation: 1 Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark.|2 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: 3 Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.|4 Harvard Medical School, Boston, MA, USA.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
mesh_terms: D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000000981:diagnostic imaging* / Q000378:metabolism; D016208:Databases, Factual; D006801:Humans; D008024:Ligands; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000378:metabolism* / Q000493:pharmacokinetics; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists
keywords: Reference region; cerebellum; serotonin (5-HT) receptors; vermis