scholarly journals Fatty Acid Amide Hydrolase Inhibition by JNJ-42165279: A Multiple-Ascending Dose and a Positron Emission Tomography Study in Healthy Volunteers

2018 ◽  
Vol 11 (4) ◽  
pp. 397-404 ◽  
Author(s):  
Andrey Postnov ◽  
Mark E. Schmidt ◽  
Darrel J. Pemberton ◽  
Jan de Hoon ◽  
Anne van Hecken ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Fatty Acid ◽  
Healthy Volunteers ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Emission Tomography ◽  
Positron Emission Tomography Study ◽  
Positron Emission ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Investigating Fatty Acid Amide Hydrolase Levels in Social Anxiety Disorder: A Positron Emission Tomography (PET) Study Using [C-11]CURB

2020 ◽  
Vol 87 (9) ◽  
pp. S299
Author(s):  
Mashal Ahmed ◽  
Rachel F. Tyndale ◽  
Dafna S. Rubin-Kahana ◽  
Bernard Le Foll ◽  
Zafiris J. Daskalakis ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Fatty Acid ◽  
Anxiety Disorder ◽  
Social Anxiety Disorder ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Emission Tomography ◽  
Positron Emission ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Voxel level quantification of [11C]CURB, a radioligand for Fatty Acid Amide Hydrolase, using high resolution positron emission tomography

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192410
Author(s):  
Pablo M. Rusjan ◽  
Dunja Knezevic ◽  
Isabelle Boileau ◽  
Junchao Tong ◽  
Romina Mizrahi ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Fatty Acid ◽  
High Resolution ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Emission Tomography ◽  
Positron Emission ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Blocking of Fatty Acid Amide Hydrolase Activity with PF-04457845 in Human Brain: A Positron Emission Tomography Study with the Novel Radioligand [11C]CURB

2015 ◽  
Vol 35 (11) ◽  
pp. 1827-1835 ◽  
Author(s):  
Isabelle Boileau ◽  
Pablo M Rusjan ◽  
Belinda Williams ◽  
Esmaeil Mansouri ◽  
Romina Mizrahi ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Fatty Acid ◽  
Human Brain ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Emission Tomography ◽  
Positron Emission ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Positron emission tomography with [11C]CURB 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 [11C]CURB 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 [11C]CURB 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 k3 (an index of FAAH activity, γ = K1/ k2) was estimated using an irreversible two-tissue compartment model with plasma input function. There were no clinically observable responses to oral PF-04457845 or [11C]CURB injection. Oral administration of PF-04457845 reduced [11C]CURB binding to a homogeneous level at all three doses, with γ k3 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 k3/[11C]CURB 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.

scholarly journals Elevated fatty acid amide hydrolase in the prefrontal cortex of borderline personality disorder: a [11C]CURB positron emission tomography study

2020 ◽  
Vol 45 (11) ◽  
pp. 1834-1841 ◽  
Author(s):  
N. J. Kolla ◽  
R. Mizrahi ◽  
K. Karas ◽  
C. Wang ◽  
R. M. Bagby ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Prefrontal Cortex ◽  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Borderline Personality ◽  
Emission Tomography ◽  
Positron Emission ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

Abstract Amygdala-prefrontal cortex (PFC) functional impairments have been linked to emotion dysregulation and aggression in borderline personality disorder (BPD). Fatty acid amide hydrolase (FAAH), the major catabolic enzyme for the endocannabinoid anandamide, has been proposed as a key regulator of the amygdala-PFC circuit that subserves emotion regulation. We tested the hypothesis that FAAH levels measured with [11C]CURB positron emission tomography in amygdala and PFC would be elevated in BPD and would relate to hostility and aggression. Twenty BPD patients and 20 healthy controls underwent FAAH genotyping (rs324420) and scanning with [11C]CURB. BPD patients were medication-free and were not experiencing a current major depressive episode. Regional differences in [11C]CURB binding were assessed using multivariate analysis of covariance with PFC and amygdala [11C]CURB binding as dependent variables, diagnosis as a fixed factor, and sex and genotype as covariates. [11C]CURB binding was marginally elevated across the PFC and amygdala in BPD (p = 0.08). In a priori selected PFC, but not amygdala, [11C]CURB binding was significantly higher in BPD (11.0%, p = 0.035 versus 10.6%, p = 0.29). PFC and amygdala [11C]CURB binding was positively correlated with measures of hostility in BPD (r > 0.4; p < 0.04). This study is the first to provide preliminary evidence of elevated PFC FAAH binding in any psychiatric condition. Findings are consistent with the model that lower endocannabinoid tone could perturb PFC circuitry that regulates emotion and aggression. Replication of these findings could encourage testing of FAAH inhibitors as innovative treatments for BPD.

scholarly journals Radiosynthesis and Evaluation of [11C-Carbonyl]-Labeled Carbamates as Fatty Acid Amide Hydrolase Radiotracers for Positron Emission Tomography

2012 ◽  
Vol 56 (1) ◽  
pp. 201-209 ◽  
Author(s):  
Alan A. Wilson ◽  
Justin W. Hicks ◽  
Oleg Sadovski ◽  
Jun Parkes ◽  
Junchao Tong ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Emission Tomography ◽  
Positron Emission ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

[11C]CURB: Evaluation of a novel radiotracer for imaging fatty acid amide hydrolase by positron emission tomography

2011 ◽  
Vol 38 (2) ◽  
pp. 247-253 ◽  
Author(s):  
Alan A. Wilson ◽  
Armando Garcia ◽  
Jun Parkes ◽  
Sylvain Houle ◽  
Junchao Tong ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Emission Tomography ◽  
Positron Emission ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

T76. Involvement of the Endocannabinoid Enzyme Fatty Acid Amide Hydrolase in the Neurobiology of Impulsivity: Positron Emission Tomography Studies With [11C]CURB

2018 ◽  
Vol 83 (9) ◽  
pp. S158
Author(s):  
Esmaeil Mansouri ◽  
Laura M. Best ◽  
Bernard Le Foll ◽  
Christian S. Hendershot ◽  
Rachel F. Tyndale ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Emission Tomography ◽  
Positron Emission ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals Lower brain fatty acid amide hydrolase in treatment-seeking patients with alcohol use disorder: a positron emission tomography study with [C-11]CURB

2020 ◽  
Vol 45 (8) ◽  
pp. 1289-1296 ◽  
Author(s):  
Laura M. Best ◽  
Belinda Williams ◽  
Bernard Le Foll ◽  
Esmaeil Mansouri ◽  
Richard P. Bazinet ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Fatty Acid ◽  
Alcohol Use Disorder ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Emission Tomography ◽  
Treatment Seeking ◽  
Positron Emission ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

scholarly journals The Fatty Acid Amide Hydrolase C385A Variant Affects Brain Binding of the Positron Emission Tomography Tracer [11C]CURB

2015 ◽  
Vol 35 (8) ◽  
pp. 1237-1240 ◽  
Author(s):  
Isabelle Boileau ◽  
Rachel F Tyndale ◽  
Belinda Williams ◽  
Esmaeil Mansouri ◽  
Duncan J Westwood ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Fatty Acid ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Emission Tomography ◽  
Positron Emission ◽  
Functional Single Nucleotide Polymorphism ◽  
Amide Hydrolase ◽  
Fatty Acid Amide

The common functional single-nucleotide polymorphism (rs324420, C385A) of the endocannabinoid inactivating enzyme fatty acid amide hydrolase (FAAH) has been associated with anxiety disorder relevant phenotype and risk for addictions. Here, we tested whether the FAAH polymorphism affects in vivo binding of the FAAH positron emission tomography (PET) probe [11C]CURB ([11C-carbonyl]-6-hydroxy-[1,10-biphenyl]-3-yl cyclohexylcarbamate (URB694)). Participants ( n = 24) completed one [11C]CURB/PET scan and were genotyped for rs324420. Relative to C/C (58%), A-allele carriers (42%) had 23% lower [11C]CURB binding ( λk3) in brain. We report evidence that the genetic variant rs324420 in FAAH is associated with measurable differences in brain FAAH binding as per PET [11C]CURB measurement.

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