%0 Journal Article
%A Elmenhorst, David
%A Kroll, Tina
%A Wedekind, Franziska
%A Weißhaupt, Angela
%A Beer, Simone
%A Bauer, Andreas
%T In Vivo Kinetic and Steady-State Quantification of 18F-CPFPX Binding to Rat Cerebral A1 Adenosine Receptors: Validation by Displacement and Autoradiographic Experiments 
%J Journal of nuclear medicine
%V 54
%N 8
%@ 0161-5505
%C Reston, Va.
%I SNM84042
%M FZJ-2013-02757
%P 1411-1419
%D 2013
%X 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. CONCLUSION: 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:23740103
%U <Go to ISI:>//WOS:000322692400055
%R 10.2967/jnumed.112.115576
%U https://juser.fz-juelich.de/record/134640