Key points are not available for this paper at this time.
Positron emission tomography with 11 CCURB was recently developed to quantify fatty acid amide hydrolase (FAAH), the enzyme responsible for hydrolyzing the endocannabinoid anandamide. This study investigated the test–retest reliability of 11 CCURB as well as its in vivo specificity and the validity of the kinetic model by using the highly specific FAAH inhibitor, PF-04457845. Five healthy volunteers completed test–retest 11 CCURB scans 1 to 2 months apart and six subjects completed baseline and blocking scans on the same day after PF-04457845 (p.o.) administration (1, 4, or 20 mg; n = 2 each). The composite parameter γ k 3 (an index of FAAH activity, γ = K 1 / k 2 ) was estimated using an irreversible two-tissue compartment model with plasma input function. There were no clinically observable responses to oral PF-04457845 or 11 CCURB injection. Oral administration of PF-04457845 reduced 11 CCURB binding to a homogeneous level at all three doses, with γ k 3 values decreased by ≥91%. Excellent reproducibility and good reliability (test–retest variability = 9%; intraclass correlation coefficient = 0.79) were observed across all regions of interest investigated. Our findings suggest that γ k 3 / 11 CCURB is a reliable, highly sensitive, and selective tool to measure FAAH activity in human brain in vivo. Moreover, PF-04457845 is a highly potent FAAH inhibitor (>95% inhibition at 1 mg) in living human brain.
Boileau et al. (Wed,) studied this question.