TAILIEUCHUNG - Moerman et al. EJNMMI Research 2011, 1:12 http://www.ejnmmires.com/content/1/1/12 PRELIMINARY

Moerman et al. EJNMMI Research 2011, 1:12 PRELIMINARY RESEARCH Open Access P-glycoprotein at the blood-brain barrier: kinetic modeling of 11C-desmethylloperamide in mice using a 18F-FDG μPET scan to determine the input function Lieselotte Moerman1*, Dieter De Naeyer2, Paul Boon3 and Filip De Vos1 Abstract Purpose: The objective of this study is the implementation of a kinetic model for 11C-desmethylloperamide (11CdLop) and the determination of a typical parameter for P-glycoprotein (P-gp) functionality in mice. Since arterial blood sampling in mice is difficult, an alternative method to obtain the arterial plasma input curve used in the kinetic model is proposed. Methods: Wild-type (WT) mice (pre-injected with saline. | Moerman et al. EJNMMI Research 2011 1 12 http content 1 1 12 9 EJNMMI Research a SpringerOpen Journal PRELIMINARY RESEARCH Open Access P-glycoprotein at the blood-brain barrier kinetic modeling of 11C-desmethylloperamide in mice using a 18F-FDG pPET scan to determine the input function Lieselotte Moerman1 Dieter De Naeyer2 Paul Boon3 and Filip De Vos1 Abstract Purpose The objective of this study is the implementation of a kinetic model for 11C-desmethylloperamide 11C-dLop and the determination of a typical parameter for P-glycoprotein P-gp functionality in mice. Since arterial blood sampling in mice is difficult an alternative method to obtain the arterial plasma input curve used in the kinetic model is proposed. Methods Wild-type WT mice pre-injected with saline or cyclosporine and P-gp knock-out KO mice were injected with 20 MBq of 11C-dLop and a dynamic pPET scan was initiated. Afterwards MBq of 18F-FDG was injected and a static pPET scan was started. An arterial input and brain tissue curve was obtained by delineation of an ROI on the left heart ventricle and the brain respectively based on the 18F-FDG scan. Results A comparison between the arterial input curves obtained by the alternative and the blood sampling method showed an acceptable agreement. The one-tissue compartment model gives the best results for the brain. In WT mice the K1 k2 ratio was while in KO mice and cyclosporine-pretreated mice the ratio was much higher and respectively . K1 can be considered as a pseudo value K1 representing a combination of passive influx of 11C-desmethylloperamide and a rapid washout by P-glycoprotein while k2 corresponds to slow passive efflux out of the brain. Conclusions An easy to implement kinetic modeling for imaging P-glycoprotein function is presented in mice without arterial blood sampling. The ratio of K1 k2 obtained from a one-tissue compartment model can be considered as a good value for P-glycoprotein .

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