Kinetic Modeling of the Monoamine Oxidase B Radioligand [11C]SL25.1188 in Human Brain with High-Resolution Positron Emission Tomography

• Published in: Journal of cerebral blood flow and metabolism Vol. 34; no. 5; pp. 883 - 889
• Main Authors: Rusjan, Pablo M, Wilson, Alan A, Miler, Laura, Fan, Ian, Mizrahi, Romina, Houle, Sylvain, Vasdev, Neil, Meyer, Jeffrey H
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.05.2014; Sage Publications Ltd; Nature Publishing Group
• Subjects: Adult; Animals; Brain - diagnostic imaging; Brain - enzymology; Carbon Radioisotopes - chemistry; Carbon Radioisotopes - metabolism; Female; Humans; Kinetics; Male; Middle Aged; Monoamine Oxidase - analysis; Monoamine Oxidase - metabolism; Original; Oxazolidinones - chemistry; Oxazolidinones - metabolism; Positron-Emission Tomography; Protein Binding; Rats; Rats, Sprague-Dawley; Young Adult; [11C]SL25.1188; reversible radioligand; modeling; MAO-B; human; PET
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1038/jcbfm.2014.34

This article describes the kinetic modeling of [11C]SL25.1188 ([(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[d]isoxazol-3-yl]-oxazolidin-2-[11C]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 [11C]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 (r2 = ≤0.9). Specific binding would account from 70% to 90% of VT. Hence, VT measurement of [11C]SL25.1 188 PET is an excellent estimation of MAO-B concentration.