title: Whole-body radiation dosimetry of 11C-carbonyl-URB694: a PET tracer for fatty acid amide hydrolase.
abstract: (11)C-carbonyl-URB694 ((11)C-CURB) is a novel (11)C-labeled suicide irreversible radiotracer for PET developed as a surrogate measure of activity of the endocannabinoid metabolizing enzyme fatty acid amide hydrolase. The aim of the study was to investigate the whole-body biodistribution and estimate the radiation dosimetry from (11)C-CURB scans in humans.
  
  
  METHODS
  Six healthy volunteers (3 men and 3 women) completed a single whole-body scan (∼120 min, 9 time frames) on a PET/CT scanner after administration of (11)C-CURB (∼350 MBq and ∼2 μg). Time-radioactivity curves were extracted in 11 manually delineated organs and corrected for injected activity, specific organ density, and volume to obtain normalized cumulated activities. OLINDA/EXM 1.1 was used to estimate standard internal dose exposure in each organ. The mean effective dose was calculated using the male and female models for the full sample and female-only sample, respectively.
  
  
  RESULTS
  (11)C-CURB was well tolerated in all subjects, with no radiotracer-related adverse event reported. The mean effective dose (±SD) was estimated to be 4.6 ± 0.3 μSv/MBq for all subjects and 5.2 ± 0.3 μSv/MBq for the female sample. Organs with the highest normalized cumulated activities (in h) were the liver (0.117), gallbladder wall (0.046), and small intestine (0.033), and organs with the highest dose exposure (in μGy/MBq) were the gallbladder wall (111 ± 60) > liver (21 ± 7), kidney (14 ± 3), and small intestine (12 ± 2).
  
  
  CONCLUSIONS
  Organ radiation exposure for the irreversible fatty acid amide hydrolase enzyme probe (11)C-CURB is within the same range as other radiotracers labeled with (11)C, thus allowing for safe, serial PET scans in the same individuals.
authors.affiliation: Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada; and Institute of Medical Science, Toronto, Ontario, Canada isabelle.boileau@CAMH.ca.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Bloomfield
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Pablo
authors.initials: P
authors.lastname: Rusjan
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Institute of Medical Science, Toronto, Ontario, Canada.
authors.forename: Romina
authors.initials: R
authors.lastname: Mizrahi
authors.affiliation: Institute of Medical Science, Toronto, Ontario, Canada.
authors.forename: Asfandyar
authors.initials: A
authors.lastname: Mufti
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Irina
authors.initials: I
authors.lastname: Vitcu
authors.affiliation: Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada; and Institute of Medical Science, Toronto, Ontario, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Human Brain Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Junchao
authors.initials: J
authors.lastname: Tong
mesh_terms: D000328:Adult; D000581:Amidohydrolases / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002219:Carbamates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D051598:Whole Body Imaging; D014916:Whole-Body Irradiation; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001713:Biphenyl Compounds; D002219:Carbamates; D019275:Radiopharmaceuticals; D000099252:Fatty Acid Amide Hydrolases; C555899:cyclohexyl carbonic acid 3'-carbamoyl-3-yl ester
keywords: 11C-CURB; dosimetry; endocannabinoid system; fatty acid amide hydrolase; positron emission tomography