title: In vivo kinetic and steady-state quantification of 18F-CPFPX binding to rat cerebral A1 adenosine receptors: validation by displacement and autoradiographic experiments.
abstract: In vivo imaging of the A1 adenosine receptor (A1AR) using (18)F-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ((18)F-CPFPX) and PET has become an important tool for studying physiologic and pathologic states of the human brain. However, dedicated experimental settings for small-animal studies are still lacking. The aim of the present study was therefore to develop and evaluate suitable pharmacokinetic models for the quantification of the cerebral A1AR in high-resolution PET.
  
  
  METHODS
  On a dedicated animal PET scanner, 15 rats underwent (18)F-CPFPX PET scans of 120-min duration. In all animals, arterial blood samples were drawn and corrected for metabolites. The radioligand was injected either as a bolus or as a bolus plus constant infusion. For the definition of unspecific binding, the A1AR selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was applied. After PET, the brains of 9 animals were dissected and in vitro saturation binding was performed using high-resolution (3)H-DPCPX autoradiography.
  
  
  RESULTS
  The kinetics of (18)F-CPFPX were well described by either compartmental or noncompartmental models based on arterial input function. The resulting distribution volume ratio correlated with a low bias toward identity with the binding potential derived from a reference region (olfactory bulb) approach. Furthermore, PET quantification correlated significantly with autoradiographic in vitro data. Blockade of the A1AR with DPCPX identified specific binding of about 45% in the reference region olfactory bulb.
  
  
  CONCLUSIONS
  The present study provides evidence that (18)F-CPFPX PET based on a reference tissue approach can be performed quantitatively in rodents in selected applications. Specific binding in the reference region needs careful consideration for quantitative investigations.
authors.affiliation: Institute of Neuroscience and Medicine, INM-2, Forschungszentrum Jülich, Jülich, Germany. d.elmenhorst@fz-juelich.de
authors.forename: David
authors.initials: D
authors.lastname: Elmenhorst
authors.forename: Tina
authors.initials: T
authors.lastname: Kroll
authors.forename: Franziska
authors.initials: F
authors.lastname: Wedekind
authors.forename: Angela
authors.initials: A
authors.lastname: Weisshaupt
authors.forename: Simone
authors.initials: S
authors.lastname: Beer
authors.forename: Andreas
authors.initials: A
authors.lastname: Bauer
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D015203:Reproducibility of Results; D014970:Xanthines / Q000378:metabolism*
chemical_list: C468796:8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine; D043682:Receptor, Adenosine A1; D014970:Xanthines
keywords: 18F-CPFPX; adenosine A1 receptor; autoradiography; blocking experiment; kinetic modeling; positron emission tomography