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P-glycoprotein at the blood-brain barrier: kinetic modeling of 11C-desmethylloperamide in mice using a 18F-FDG µPET scan to determinate the input function

Lieselotte Moerman (UGent) , Dieter De Naeyer (UGent) , Paul Boon (UGent) and Filip De Vos (UGent)
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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 or cyclosporine) and P-gp knock-out (KO) mice were injected with 20 MBq of 11C-dLop, and a dynamic μPET scan was initiated. Afterwards, 18.5 MBq of 18F-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 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 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). 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 functionality.

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Chicago
Moerman, Lieselotte, Dieter De Naeyer, Paul Boon, and Filip De Vos. 2011. “P-glycoprotein at the Blood-brain Barrier: Kinetic Modeling of 11C-desmethylloperamide in Mice Using a 18F-FDG µPET Scan to Determinate the Input Function.” Ejnmmi Research 1.
APA
Moerman, L., De Naeyer, D., Boon, P., & De Vos, F. (2011). P-glycoprotein at the blood-brain barrier: kinetic modeling of 11C-desmethylloperamide in mice using a 18F-FDG µPET scan to determinate the input function. EJNMMI RESEARCH, 1.
Vancouver
1.
Moerman L, De Naeyer D, Boon P, De Vos F. P-glycoprotein at the blood-brain barrier: kinetic modeling of 11C-desmethylloperamide in mice using a 18F-FDG µPET scan to determinate the input function. EJNMMI RESEARCH. 2011;1.
MLA
Moerman, Lieselotte, Dieter De Naeyer, Paul Boon, et al. “P-glycoprotein at the Blood-brain Barrier: Kinetic Modeling of 11C-desmethylloperamide in Mice Using a 18F-FDG µPET Scan to Determinate the Input Function.” EJNMMI RESEARCH 1 (2011): n. pag. Print.
@article{1984308,
  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 or cyclosporine) and P-gp knock-out (KO) mice were injected with 20 MBq of 11C-dLop, and a dynamic \ensuremath{\mu}PET scan was initiated. Afterwards, 18.5 MBq of 18F-FDG was injected, and a static \ensuremath{\mu}PET 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 0.4 {\textpm} 0.1, while in KO mice and cyclosporine-pretreated mice the ratio was much higher (2.0 {\textpm} 0.4 and 1.9 {\textpm} 0.2, 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 functionality.},
  articleno    = {12},
  author       = {Moerman, Lieselotte and De Naeyer, Dieter and Boon, Paul and De Vos, Filip},
  issn         = {2191-219X},
  journal      = {EJNMMI RESEARCH},
  language     = {eng},
  pages        = {9},
  title        = {P-glycoprotein at the blood-brain barrier: kinetic modeling of 11C-desmethylloperamide in mice using a 18F-FDG {\textmu}PET scan to determinate the input function},
  url          = {http://dx.doi.org/10.1186/2191-219X-1-12},
  volume       = {1},
  year         = {2011},
}

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