title: Kinetic modeling of the monoamine oxidase B radioligand [¹¹C]SL25.1188 in human brain with high-resolution positron emission tomography.
abstract: This article describes the kinetic modeling of [(11)C]SL25.1188 ([(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[d]isoxazol-3-yl]-oxazolidin-2-[(11)C]one]) binding to monoamine oxidase B (MAO-B) in the human brain using high-resolution positron emission tomography (PET). Seven healthy subjects underwent two separate 90- minute PET scans after an intravenous injection of [(11)C]SL25.1188. Complementary arterial blood sampling was acquired. Radioactivity was quickly eliminated from plasma with 80% of parent compound remaining at 90 minutes. Metabolites were more polar than the parent compound. Time-activity curves showed high brain uptake, early peak and washout rate consistent with known regional MAO-B concentration. A two-tissue compartment model (2-TCM) provided better fits to the data than a 1-TCM. Measurement of total distribution volume (VT) showed very good identifiability (based on coefficient of variation (COV)) for all regions of interest (ROIs) (COV(VT)<8%), low between-subject variability (∼20%), and quick temporal convergence (within 5% of final value at 45 minutes). Logan graphical method produces very good estimation of VT. Regional VT highly correlated with previous postmortem report of MAO-B level (r(2)= ≥ 0.9). Specific binding would account from 70% to 90% of VT. Hence, VT measurement of [(11)C]SL25.1(1)88 PET is an excellent estimation of MAO-B concentration.
authors: Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada.
authors: Pablo M
authors: PM
authors: Rusjan
authors: 1] Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors: Alan A
authors: AA
authors: Wilson
authors: Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada.
authors: Laura
authors: L
authors: Miler
authors: Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada.
authors: Ian
authors: I
authors: Fan
authors: 1] Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors: Romina
authors: R
authors: Mizrahi
authors: 1] Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors: Sylvain
authors: S
authors: Houle
authors: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, and Department of Radiology, Harvard Medical School, Boston, Massachusetts, USA.
authors: Neil
authors: N
authors: Vasdev
authors: 1] Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors: Jeffrey H
authors: JH
authors: Meyer
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000201:enzymology*; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000032:analysis* / Q000378:metabolism; D023303:Oxazolidinones / Q000737:chemistry / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D023303:Oxazolidinones; D008995:Monoamine Oxidase