title: [123I]AM281 single-photon emission computed tomography imaging of central cannabinoid CB1 receptors before and after Delta9-tetrahydrocannabinol therapy and whole-body scanning for assessment of radiation dose in tourette patients.
abstract: BACKGROUND
  The cannabinoid CB1 receptor agonist Delta9-THC has been suggested for treatment of Tourette syndrome (TS). Based on animal studies, the CB1 antagonist [123I]AM281 (N-(Morpholin-4-yl)-1-(2,4-dichlorophenyl)-5-(4-[123I]iodophenyl)-4-methyl-1H-pyrazole-3-carboxamide) has been proposed for single photon emission computed tomography (SPECT) in humans. Our aims were to 1) evaluate specific binding of [123I]AM281 to CB1 receptors in TS patients and 2) assess radiation exposure associated with the use of AM281 labeled with 123I for SPECT and 124I for positron emission tomography.
  
  
  METHODS
  We employed [123I]AM281 in six TS patients before and after Delta9-THC treatment. Dynamic SPECT, plasma measurements (including metabolite analysis with thin layer chromatography), and whole-body imaging were performed. Regions of interest derived from magnetic resonance images were used to extract from SPECT uptake in an area with high CB1 density (lentiform nuclei) and reference regions. Specific over nonspecific partition coefficients V3" were calculated. Whole-body images were carried out for dosimetric analysis. Data obtained with [123I]AM281 were used to predict doses from [124I]AM281.
  
  
  RESULTS
  Mean V3" ranged from .19 to .31 and did not change significantly after Delta9-THC treatment. Nevertheless, in the only patient with a marked clinical response, V3" clearly declined. Thin layer chromatography revealed biexponential kinetics of tracer metabolism; about 60% remained nonmetabolized after 3 hours. Effective doses of .011 mSv/MBq for [123I]AM281 and .34 for [124I]AM281 were computed.
  
  
  CONCLUSIONS
  This study suggests that specific binding of [123I]AM281 to CB1 receptors can be detected in patients using SPECT. Radiation exposure with [123I]AM281 is low; that with [124I]AM281 is higher but acceptable for single investigations.
authors.affiliation: Nuclear Medicine, University School of Medicine, Hannover, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Berding
authors.forename: Kirsten
authors.initials: K
authors.lastname: Müller-Vahl
authors.forename: Udo
authors.initials: U
authors.lastname: Schneider
authors.forename: Peter
authors.initials: P
authors.lastname: Gielow
authors.forename: Jürgen
authors.initials: J
authors.lastname: Fitschen
authors.forename: Manfred
authors.initials: M
authors.lastname: Stuhrmann
authors.forename: Heinrich
authors.initials: H
authors.lastname: Harke
authors.forename: Ralph
authors.initials: R
authors.lastname: Buchert
authors.forename: Frank
authors.initials: F
authors.lastname: Donnerstag
authors.forename: Michael
authors.initials: M
authors.lastname: Hofmann
authors.forename: Bernd O
authors.initials: BO
authors.lastname: Knoop
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Hinderk M
authors.initials: HM
authors.lastname: Emrich
authors.forename: Wolfram H
authors.initials: WH
authors.lastname: Knapp
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology; D002855:Chromatography, Thin Layer; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D005879:Tourette Syndrome / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D051598:Whole Body Imaging
chemical_list: D011619:Psychotropic Drugs; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1; C072823:delta9-tetrahydrocannabinol hemisuccinate; D013759:Dronabinol