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

Journal of Nuclear Medicine

Angela Weisshaupt¹  David Elmenhorst¹  Andreas Bauer¹  Simone Beer¹  Tina Kroll¹  Franziska Wedekind¹ 

关键词: positron emission tomography;    autoradiography;    blocking experiment;    kinetic modeling;    ¹⁸F-CPFPX;    adenosine A₁ receptor;   

DOI  :  10.2967/jnumed.112.115576

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown