Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 33, Issue 3, Pages 407-414Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2012.180
Keywords
[C-11]CURB; endocannabinoid; FAAH; fatty acid amide hydrolase; kinetic modeling; PET; positron emission tomography
Categories
Funding
- Canada Foundation for Innovation
- Ontario Ministry of Research and Innovation
Ask authors/readers for more resources
Endocannabinoid tone has recently been implicated in a number of prevalent neuropsychiatric conditions. [C-11]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 [C-11]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 lambda k(3) (lambda=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 lambda k(3). Our data suggest that lambda k(3) is sensitive to changes in FAAH activity, therefore, optimal for PET quantification of FAAH activities with [C-11]CURB. Simulations showed that [C-11]CURB binding in healthy subjects is far from a flow-limited uptake. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 407-414; doi: 10.1038/jcbfm.2012.180; published online 5 December 2012
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available