In Vivo Kinetic and Steady-State Quantification of 18F-CPFPX Binding to Rat Cerebral A1 Adenosine Receptors: Validation by Displacement and Autoradiographic Experiments

D. Elmenhorst, T. Kroll, F. Wedekind, A. Weisshaupt, S. Beer, A. Bauer
2013 Journal of Nuclear Medicine  
In vivo imaging of the A 1 adenosine receptor (A 1 AR) using 18 F-8cyclopentyl-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 A 1 AR in high-resolution PET. Methods: On
more » ... 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 A 1 AR 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 A 1 AR 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.
doi:10.2967/jnumed.112.115576 pmid:23740103 fatcat:bi3m6fojb5h45hh36rvamjdsnm