PT  - JOURNAL ARTICLE
AU  - David Elmenhorst
AU  - Tina Kroll
AU  - Franziska Wedekind
AU  - Angela Weisshaupt
AU  - Simone Beer
AU  - Andreas Bauer
TI  - In Vivo Kinetic and Steady-State Quantification of <sup>18</sup>F-CPFPX Binding to Rat Cerebral A<sub>1</sub> Adenosine Receptors: Validation by Displacement and Autoradiographic Experiments
AID  - 10.2967/jnumed.112.115576
DP  - 2013 Aug 01
TA  - Journal of Nuclear Medicine
PG  - 1411--1419
VI  - 54
IP  - 8
4099  - http://jnm.snmjournals.org/content/54/8/1411.short
4100  - http://jnm.snmjournals.org/content/54/8/1411.full
SO  - J Nucl Med2013 Aug 01; 54
AB  - In vivo imaging of the A1 adenosine receptor (A1AR) using 18F-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (18F-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 18F-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 3H-DPCPX autoradiography. Results: The kinetics of 18F-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 18F-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.