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000134640 1001_ $$0P:(DE-Juel1)131679$$aElmenhorst, David$$b0$$eCorresponding author$$ufzj
000134640 245__ $$aIn Vivo Kinetic and Steady-State Quantification of 18F-CPFPX Binding to Rat Cerebral A1 Adenosine Receptors: Validation by Displacement and Autoradiographic Experiments 
000134640 260__ $$aReston, Va.$$bSNM84042$$c2013
000134640 264_1 $$2Crossref$$3online$$bSociety of Nuclear Medicine$$c2013-06-05
000134640 264_1 $$2Crossref$$3print$$bSociety of Nuclear Medicine$$c2013-08-01
000134640 264_1 $$2Crossref$$3print$$bSociety of Nuclear Medicine$$c2013-08-01
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000134640 520__ $$aIn 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.
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000134640 7001_ $$0P:(DE-Juel1)131691$$aKroll, Tina$$b1$$ufzj
000134640 7001_ $$0P:(DE-Juel1)131711$$aWedekind, Franziska$$b2
000134640 7001_ $$0P:(DE-Juel1)131712$$aWeißhaupt, Angela$$b3
000134640 7001_ $$0P:(DE-Juel1)133864$$aBeer, Simone$$b4$$ufzj
000134640 7001_ $$0P:(DE-Juel1)131672$$aBauer, Andreas$$b5$$ufzj
000134640 77318 $$2Crossref$$3journal-article$$a10.2967/jnumed.112.115576$$b : Society of Nuclear Medicine, 2013-06-05$$n8$$p1411-1419$$tJournal of Nuclear Medicine$$v54$$x0161-5505$$y2013
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