title: Quantitative imaging of neuroinflammation in human white matter: a positron emission tomography study with translocator protein 18 kDa radioligand, [18F]-FEPPA.
abstract: The ability to quantify translocator protein 18 kDa (TSPO) in white matter (WM) is important to understand the role of neuroinflammation in neurological disorders with WM involvement. This article aims to extend the utility of TSPO imaging in WM using a second-generation radioligand, [18F]-FEPPA, and high-resolution research tomograph (HRRT) positron emission tomography (PET) camera system. Four WM regions of interests (WM-ROI), relevant to the study of aging and neuroinflammatory diseases, were examined. The corpus callosum, cingulum bundle, superior longitudinal fasciculus, and posterior limb of internal capsule were delineated automatically onto subject's T1 -weighted magnetic resonance image using a diffusion tensor imaging-based WM template. The TSPO polymorphism (rs6971) stratified individuals to three genetic groups: high-affinity binders (HAB), mixed-affinity binders (MAB), and low-affinity binders. [18F]-FEPPA PET scans were acquired on 32 healthy subjects and analyzed using a full kinetic compartment analysis. The two-tissue compartment model showed moderate identifiability (coefficient of variation 15-19%) for [18F]-FEPPA total volume distribution (VT ) in WM-ROIs. Noise affects VT variability, although its effect on bias was small (6%). In a worst-case scenario, ≤6% of simulated data did not fit reliably. A simulation of increased TSPO density exposed minimal effect on variability and identifiability of [18F]-FEPPA VT in WM-ROIs. We found no association between age and [18F]-FEPPA VT in WM-ROIs. The VT values were 15% higher in HAB than in MAB, although the difference was not statistically significant. This study provides evidence for the utility and limitations of [18F]-FEPPA PET to measure TSPO expression in WM.
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8, Canada; Institute of Medical Science, University of Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Suridjan
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Rusjan
authors.forename: Miran
authors.initials: M
authors.lastname: Kenk
authors.forename: Nicolaas Paul L G
authors.initials: NP
authors.lastname: Verhoeff
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
authors.forename: David
authors.initials: D
authors.lastname: Rotenberg
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Romina
authors.initials: R
authors.lastname: Mizrahi
mesh_terms: D000328:Adult; D000368:Aged; D000813:Anilides / Q000493:pharmacokinetics*; D003337:Corpus Callosum / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011725:Pyridines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D066127:White Matter / Q000000981:diagnostic imaging*
chemical_list: D000813:Anilides; C530438:N-(2-((N-(4-phenoxypyridin-3-yl)acetamido)methyl)phenoxy)ethyl fluoride; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: [18F]-FEPPA; neuroinflammation; positron emission tomography imaging; translocator protein; white matter