title: Comparison of standardized uptake values with volume of distribution for quantitation of [(11)C]PBR28 brain uptake.
abstract: BACKGROUND
  [(11)C]PBR28 is a high-affinity ligand for the Translocator Protein 18 kDa (TSPO), which is considered to be a marker for microglial activation. Volume of distribution (VT) estimated with an arterial plasma input function is the gold standard for quantitation of [(11)C]PBR28 binding. However, arterial sampling is impractical at many PET sites for multiple reasons. Reference region modeling approaches are not ideal for TSPO tracers, as the existence of a true reference region cannot be assumed. Given that it would be desirable to have a non-invasive index of [(11)C]PBR28 binding, we elected to study the utility of the semi-quantitative metric, standardized uptake value (SUV) for use in brain [(11)C]PBR PET studies. The primary goal of this study was to determine the relationship between SUV and VT.
  
  
  METHODS
  We performed a retrospective analysis of data from sixteen [(11)C]PBR28 PET scans acquired in baboons at baseline and at multiple time points after IV injection of lipopolysaccharide, an endotoxin that transiently induces neuroinflammation. For each scan, data from 14 brain regions of interest were studied. VT was estimated with the Logan plot, using metabolite-corrected input functions. SUV was calculated with data from 30 to 60 minutes after [(11)C]PBR28 injection.
  
  
  RESULTS
  Within individual PET studies, SUV tended to correlate well with VT. Across studies, the relationship between SUV and VT was variable.
  
  
  CONCLUSIONS
  From study to study, there was variability in the degree of correlation between [(11)C]PBR28 VT and SUV. There are multiple physiological factors that may contribute to this variance.
  
  
  CONCLUSIONS
  As currently applied, the non-invasive measurement of SUV does not appear to be a reliable outcome variable for [(11)C]PBR28. Additional work is needed to discover the source of the discrepancy in SUV between [(11)C]PBR28 scans.
  
  
  CONCLUSIONS
  There is a need to develop alternatives to arterial plasma input functions for TSPO ligands in order to facilitate multi-center trials.
authors.affiliation: Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis IN; Center for Neuroimaging, Indiana University School of Medicine, Indianapolis IN; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN. Electronic address: kkyoder@iupui.edu.
authors.forename: Karmen K
authors.initials: KK
authors.lastname: Yoder
authors.affiliation: Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis IN.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Territo
authors.affiliation: Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis IN; Center for Neuroimaging, Indiana University School of Medicine, Indianapolis IN.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
authors.affiliation: Yale PET Center, Yale University School of Medicine, New Haven CT.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hannestad
authors.affiliation: Yale PET Center, Yale University School of Medicine, New Haven CT.
authors.forename: Evan D
authors.initials: ED
authors.lastname: Morris
authors.affiliation: Yale PET Center, Yale University School of Medicine, New Haven CT.
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.affiliation: Center for Advanced Medical Imaging Sciences, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston MA.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Normandin
authors.affiliation: Yale PET Center, Yale University School of Medicine, New Haven CT.
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010215:Papio; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011743:Pyrimidines / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism; D012015:Reference Standards
chemical_list: C526315:(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; D008070:Lipopolysaccharides; D011743:Pyrimidines; D018079:Receptors, GABA
keywords: Inflammation; PBR28; PET; SUV; TSPO; Validity