title: Radiation Dosimetry of a Novel Adenosine A2AReceptor Radioligand [11C]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats.
abstract: [11C]Preladenant was developed as a novel adenosine A2Areceptor PET radioligand. The aim of this study was to determine the radiation dosimetry of [11C]preladenant and to investigate whether dosimetry estimation based on organ harvesting can be replaced by positron emission tomography (PET)/x-ray computed tomography (CT) imaging in rats.
  
  
  
  Male Wistar rats (n = 35) were i.v. injected with [11C]preladenant. The tracer biodistribution was determined by organ harvesting at 1, 5, 15, 30, 60, and 90 min post injection. Hollow organs including the stomach, intestines, and urinary bladder were harvested with contents. In 10 rats, a 90-min dynamic PET/CT scan of the torso was acquired. Twenty volumes of interest (VOIs) were manually drawn on the PET image using the CT image of the same animal as anatomical reference. The dynamic time-activity curves were used to calculate organ residence times (RTs). Human radiation dosimetry estimates, derived from rat data, were calculated with OLINDA/EXM 1.1.
  
  
  
  PET-imaging and organ-harvesting estimated comparable organ RTs, with differences of 6-27 %, except for the lungs, pancreas, and urinary bladder, with differences of 48, 53, and 60, respectively. The critical organ was the small intestine with a dose of 25 μSv/MBq. The effective doses (EDs) calculated from imaging-based and organ-harvesting-derived data were 5.5 and 5.6 μSv/MBq, respectively, using the International Commission on Radiological Protection 60 tissue weighting factors.
  
  
  
  The ED of [11C]preladenant (2 mSv for a 370-MBq injected dose) is comparable with other C-11-labeled PET tracers. Estimation of the radiation dosimetry of [11C]preladenant by PET/CT imaging in rats is feasible and gives comparable results to organ harvesting, provided that small VOIs are used and the content of hollow organs is taken into account. Dosimetry by PET imaging can strongly reduce the number of laboratory animals required.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Shivashankar
authors.initials: S
authors.lastname: Khanapur
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Erik F J
authors.initials: EF
authors.lastname: de Vries
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. j.r.de.jong@umcg.nl.
authors.forename: Johan R
authors.initials: JR
authors.lastname: de Jong
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000737:chemistry*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011743:Pyrimidines / Q000737:chemistry*; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D014018:Tissue Distribution; D014230:Triazoles / Q000737:chemistry*
chemical_list: D002250:Carbon Radioisotopes; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D043705:Receptor, Adenosine A2A; D014230:Triazoles; C539997:2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine
keywords: Adenosine A2A receptor; Radiation dosimetry; Rat; Small-animal PET/CT; [11C]preladenant