TY  - JOUR
AU  - Elmenhorst, David
AU  - Kroll, Tina
AU  - Wedekind, Franziska
AU  - Weißhaupt, Angela
AU  - Beer, Simone
AU  - Bauer, Andreas
TI  - In Vivo Kinetic and Steady-State Quantification of 18F-CPFPX Binding to Rat Cerebral A1 Adenosine Receptors: Validation by Displacement and Autoradiographic Experiments 
JO  - Journal of nuclear medicine
VL  - 54
IS  - 8
SN  - 0161-5505
CY  - Reston, Va.
PB  - SNM84042
M1  - FZJ-2013-02757
SP  - 1411-1419
PY  - 2013
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:23740103
UR  - <Go to ISI:>//WOS:000322692400055
DO  - DOI:10.2967/jnumed.112.115576
UR  - https://juser.fz-juelich.de/record/134640
ER  -