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

Mapping Human Brain Fatty Acid Amide Hydrolase Activity with PET

“…Similar to the observation in rats, 2 the radiometabolites eluted earlier than [ 11 C]CURB, indicating that CBF, cerebral blood flow; SA, specific activity. CBF is the measure using the technique of continuous arterial spin labeling and average in a region including cortical gray matter, striatal gray matter, and cerebellum gray matter.…”

“…2 The method utilizes a novel one-pot automated [ approved by the Research Ethics Board of CAMH and authorized by Health Canada. All subjects provided written informed consent after the procedures were fully explained to them.…”

“…In this regard, a number of highly specific and potent FAAH inhibitors have been discovered, including the prototypical carbamate inhibitor URB597, which have provided the basis for development of suitable radiotracers for PET imaging of FAAH. We recently reported 1,2 the radiolabeling of a close analog of URB597, 6-hydroxy- [ 2 show that (1) regional brain uptake of [ 11 C]CURB corresponds with the known distribution of FAAH in rat brain, specifically greater uptake is noted in cerebral cortex, cerebellum, and hippocampus with lowest uptake in the FAAH poor hypothalamus region; (2) administration of the unlabeled FAAH inhibitors URB694 and URB597 decreases brain uptake of [ 11 C]CURB in a dose-dependent manner; (3) binding of the radiotracer in the brain is irreversible based on chromatographic analyses of the fate of the radiolabel; and (4) the metabolites in blood, more polar than the parent compound, are unlikely to cross the blood-brain barrier.…”

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

“…We recently reported the synthesis of [ 11 C]CURB ([ 11 C-carbonyl]-6-hydroxy-[1,10-biphenyl]-3-yl cyclohexylcarbamate (URB694)), 26 the first available positron emission tomography (PET) radiotracer for imaging FAAH, and showed that a two-tissue compartment 1 model with irreversible trapping (2-TCMi) fitted the regional timeactivity curves (TACs) measured in vivo in the human brain. 27 The composite parameter λk 3 (λ = K 1 /k 2 ) was recommended as the preferred index for PET quantification of FAAH activity given its high identifiability and direct proportion to the irreversible trapping rate constant k 3 .…”

Whole-Body Radiation Dosimetry of 11C-Carbonyl-URB694: A PET Tracer for Fatty Acid Amide Hydrolase

“…The potential of 11 C-CURB as a radiotracer to image FAAH in humans has already been shown (8); however, the radiation dosimetry estimates for those studies had been obtained by extrapolation from rat studies (7). This study provides updated dose estimates based on biodistribution data obtained directly in humans.…”