title: Human biodistribution and dosimetry of 18F-JNJ42259152, a radioligand for phosphodiesterase 10A imaging.
abstract: OBJECTIVE
  Phosphodiesterase 10A (PDE10A) is a cAMP/cGMP-hydrolysing enzyme with a central role in striatal signalling and implicated in neuropsychiatric disorders such as Huntington's disease, Parkinson's disease, schizophrenia and addiction. We have developed a novel PDE10A PET ligand, (18)F-JNJ42259152, and describe here its human dynamic biodistribution, safety and dosimetry.
  
  
  METHODS
  Six male subjects (age range 23-67 years) underwent ten dynamic whole-body PET/CT scans over 6 h after bolus injection of 175.5 ± 9.4 MBq (18)F-JNJ42259152. Source organs were delineated on PET/CT and individual organ doses and effective dose were determined using the OLINDA software.
  
  
  RESULTS
  F-JNJ42259152 was readily taken up by the brain and showed exclusive retention in the brain, especially in the striatum with good washout starting after 20 min. The tracer was cleared through both the hepatobiliary and the urinary routes. No defluorination was observed. Organ absorbed doses were largest for the gallbladder (239 μSv/MBq) and upper large intestine (138 μSv/MBq). The mean effective dose was 24.9 ± 4.1 μSv/MBq. No adverse events were encountered.
  
  
  CONCLUSIONS
  In humans, (18)F-JNJ42259152 has an appropriate distribution, brain kinetics and safety. The estimated effective dose was within WHO class IIb with low interindividual variability. Therefore, the tracer is suitable for further kinetic evaluation in humans.
authors.affiliation: Division of Nuclear Medicine, University Hospital Leuven and KU Leuven, Leuven, Belgium. koen.vanlaere@uzleuven.be
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.forename: Rawaha U
authors.initials: RU
authors.lastname: Ahmad
authors.forename: Hendra
authors.initials: H
authors.lastname: Hudyana
authors.forename: Sofie
authors.initials: S
authors.lastname: Celen
authors.forename: Kristof
authors.initials: K
authors.lastname: Dubois
authors.forename: Mark E
authors.initials: ME
authors.lastname: Schmidt
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D005462:Fluorine Radioisotopes / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008024:Ligands; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D013997:Time Factors; D051598:Whole Body Imaging / Q000379:methods
chemical_list: C581925:2-((4-(1-(2-fluoroethyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl)phenoxy)methyl)-3,5-dimethylpyridine; D005462:Fluorine Radioisotopes; D008024:Ligands; D011720:Pyrazoles; D011725:Pyridines; D019275:Radiopharmaceuticals; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases