title: Mapping human brain fatty acid amide hydrolase activity with PET.
abstract: Endocannabinoid tone has recently been implicated in a number of prevalent neuropsychiatric conditions. [(11)C]CURB is the first available positron emission tomography (PET) radiotracer for imaging fatty acid amide hydrolase (FAAH), the enzyme which metabolizes the prominent endocannabinoid anandamide. Here, we sought to determine the most suitable kinetic modeling approach for quantifying [(11)C]CURB that binds selectively to FAAH. Six healthy volunteers were scanned with arterial blood sampling for 90 minutes. Kinetic parameters were estimated regionally using a one-tissue compartment model (TCM), a 2-TCM with and without irreversible trapping, and an irreversible 3-TCM. The 2-TCM with irreversible trapping provided the best identifiability of PET outcome measures among the approaches studied (coefficient of variation (COV) of the net influx constant K(i) and the composite parameter λk(3) (λ=K(1)/k(2)) <5%, and COV(k(3))<10%). Reducing scan time to 60 minutes did not compromise the identifiability of rate constants. Arterial spin labeling measures of regional cerebral blood flow were only slightly correlated with K(i), but not with k(3) or λk(3). Our data suggest that λk(3) is sensitive to changes in FAAH activity, therefore, optimal for PET quantification of FAAH activities with [(11)C]CURB. Simulations showed that [(11)C]CURB binding in healthy subjects is far from a flow-limited uptake.
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. pablo.rusjan@camhpet.ca
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Rusjan
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Romina
authors.initials: R
authors.lastname: Mizrahi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.forename: Sofia E
authors.initials: SE
authors.lastname: Chavez
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Lobaugh
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Junchao
authors.initials: J
authors.lastname: Tong
mesh_terms: D000328:Adult; D000581:Amidohydrolases / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011859:Radiography; D013113:Spin Labels; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D009419:Nerve Tissue Proteins; D013113:Spin Labels; D000099252:Fatty Acid Amide Hydrolases