Quantitation of translocator protein binding in human brain with the novel radioligand [18F]-FEPPA and positron emission tomography

This article describes the kinetic modeling of [F-18]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume (V-T), specific distribution volume (V-S), and binding potential (BPND) demonstrated very good identifiability (based on coefficient of variation (COV)) for all the regions of interest (ROIs) in the gray matter (COV V-T < 7%, COV V-S < 8%, COV BPND < 11%). Reduction of the length of the scan to 2 hours is feasible as V-S and V-T showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of V-T and V-S was still very good with COV < 10%, across high-uptake ROIs. The excellent identifiability of V-T values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of V-T as an appropriate and feasible outcome measure for [F-18]-FEPPA. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1807-1816; doi:10.1038/jcbfm.2011.55; published online 27 April 2011