Kinetic Analysis of the Cannabinoid-1 Receptor PET Tracer [18F] MK-9470 in Human Brain

PURPOSE: Quantitative imaging of the type 1 cannabinoid receptor (CB1R) opens perspectives for many neurological and psychiatric disorders. We characterized the kinetics and reproducibility of the CB1R tracer [(18)F]MK-9470 in human brain. METHODS: [(18)F]MK-9470 data were analysed using reversible models and the distribution volume V (T) and V (ND) k (3) (V (ND) k (3) = K (1) k (2)) were estimated. Tracer binding was also evaluated using irreversible kinetics and the irreversible uptake constant K (i) and fractional uptake rate (FUR) were estimated. The effect of blood flow on these parameters was evaluated. Additionally, the possibility of determining the tracer plasma kinetics using a reduced number of blood samples was also examined. RESULTS: A reversible two-tissue compartment model using a global k (4) value was necessary to describe brain kinetics. Both V (T) and V (ND) k (3) were estimated satisfactorily and their test-retest variability was between 10% and 30%. Irreversible methods adequately described brain kinetics and FUR values were equivalent to K (i). The linear relationship between K (i) and V (ND) k (3) demonstrated that K (i) or FUR and thus the simple measure of tracer brain uptake provide CB1R availability information. The test-retest variability of K (i) and FUR was