Document Detail


Mapping human brain fatty acid amide hydrolase activity with PET.
MedLine Citation:
PMID:  23211960     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Pablo M Rusjan; Alan A Wilson; Romina Mizrahi; Isabelle Boileau; Sofia E Chavez; Nancy J Lobaugh; Stephen J Kish; Sylvain Houle; Junchao Tong
Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-05
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-01     Completed Date:  2013-04-19     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  407-14     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Amidohydrolases / metabolism*
Brain / metabolism*,  radiography
Brain Mapping / methods*
Computer Simulation
Female
Humans
Kinetics
Male
Middle Aged
Models, Biological*
Nerve Tissue Proteins / metabolism*
Positron-Emission Tomography / methods*
Spin Labels
Chemical
Reg. No./Substance:
0/Nerve Tissue Proteins; 0/Spin Labels; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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