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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 ?k(3) (?=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 ?k(3). Our data suggest that ?k(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.

SUBMITTER: Rusjan PM 

PROVIDER: S-EPMC3587811 | biostudies-other | 2013 Mar

REPOSITORIES: biostudies-other

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Mapping human brain fatty acid amide hydrolase activity with PET.

Rusjan Pablo M PM   Wilson Alan A AA   Mizrahi Romina R   Boileau Isabelle I   Chavez Sofia E SE   Lobaugh Nancy J NJ   Kish Stephen J SJ   Houle Sylvain S   Tong Junchao J  

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20121205 3


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 samplin  ...[more]

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