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.
Measurement of human cerebral monoamine oxidase type B (MAO-B) activity with positron emission tomography (PET): a dose ranging study with the reversible inhibitor Ro 19-6327