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Purpose  The objective of this study is the implementation of a kinetic model for  11 C-desmethylloperamide ( 11 C-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  11 C-dLop, and a dynamic μPET scan was initiated. Afterwards, 18.5 MBq of  18 F-FDG was injected, and a static μPET 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  18 F-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  K  1 / k  2  ratio was 0.4 ± 0.1, while in KO mice and cyclosporine-pretreated mice the ratio was much higher (2.0 ± 0.4 and 1.9 ± 0.2, respectively).  K  1  can be considered as a pseudo value  K  1 , representing a combination of passive influx of  11 C-desmethylloperamide and a rapid washout by P-glycoprotein, while  k  2  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  K  1 / k  2  obtained from a one-tissue compartment model can be considered as a good value for P-glycoprotein functionality.

ejnmmi research

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