Kinetic modeling of the monoamine oxidase B radioligand [11C]SL25.1188 in human brain with high-resolution positron emission tomography

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 (V_T) showed very good identifiability (based on coefficient of variation (COV)) for all regions of interest (ROIs) (COV(V_T)<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 V_T. Regional V_T highly correlated with previous postmortem report of MAO-B level (r²=⩾0.9). Specific binding would account from 70% to 90% of V_T. Hence, V_T measurement of [¹¹C]SL25.1¹88 PET is an excellent estimation of MAO-B concentration.