Kinetic Analysis of the Metabotropic Glutamate Subtype 5 Tracer [18F]FPEB in Bolus and Bolus-Plus-Constant-Infusion Studies in Humans. Issue 4 (April 2013)

• Record Type: Journal Article
• Authors: Sullivan, Jenna M; Lim, Keunpoong; Labaree, David; Lin, Shu-fei; McCarthy, Timothy J; Seibyl, John P; Tamagnan, Gilles; Huang, Yiyun; Carson, Richard E; Ding, Yu-Shin; Morris, Evan D
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 33:Issue 4(2013)
• Page Start: 532
• Page End: 541
• Publication Date: 2013-04
• Subjects: binding potential (BPND) -- bolus-plus-constant-infusion -- glutamate -- mGluR5 -- scan duration -- total volume of distribution (VT); Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1038/jcbfm.2012.195
• Languages: English
• ISSNs: 0271-678X

Abstract

[ 18 F]FPEB is a positron emission tomography tracer which, in preclinical studies, has shown high specificity and selectivity toward the metabotropic glutamate receptor 5 (mGluR5). It possesses the potential to be used in human studies to evaluate mGluR5 function in a range of neuropsychiatric disorders, such as anxiety and Fragile X syndrome. To define optimal scan methodology, healthy human subjects were scanned for 6 hours following either a bolus injection ( n = 5) or bolus-plus-constant-infusion ( n = 5) of [ 18 F]FPEB. Arterial blood samples were collected and parent fraction measured by high-performance liquid chromatography (HPLC) to determine the metabolite-corrected plasma input function. Time activity curves were extracted from 13 regions and fitted by various models to estimate V T and BP ND . [ 18 F]FPEB was well fitted by the two-tissue compartment model, MA1 ( t ∗ = 30), and MRTM (using cerebellum white matter as a reference). Highest V T values were observed in the anterior cingulate and caudate, and lowest V T values were observed in the cerebellum and pallidum. For kinetic modeling studies, V T and BP ND were estimated from bolus or bolus-plus-constant-infusion scans as short as 90 minutes. Bolus-plus-constant-infusion of [ 18 F]FPEB reduced intersubject variability in V T and allowed equilibrium analysis to be completed with a 30-minute scan, acquired 90–120 minutes after the start of injection.