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Imaging P-glycoprotein function in rats using [(11)C]-N-desmethyl-loperamide.

Michael D Farwell1, Derek J Chong, Yasuhiko Iida

  • 1Department of Radiology, Columbia University Medical Center, 180 Fort Washington Ave. HP 3-305, New York, NY 10032, USA. mdf2104@columbia.edu

Annals of Nuclear Medicine
|April 11, 2013
PubMed
Summary

The novel P-glycoprotein (P-gp) PET tracer, [(11)C]N-desmethyl-loperamide ([(11)C]dLop), shows increased brain uptake after P-gp inhibition. This tracer is promising for measuring P-gp function in epilepsy research.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Radiochemistry

Background:

  • Epilepsy drug resistance may involve P-glycoprotein (P-gp) upregulation.
  • P-gp acts as a drug efflux pump at the epileptogenic focus.
  • Developing tools to measure P-gp function is crucial for understanding drug resistance.

Purpose of the Study:

  • To evaluate [(11)C]N-desmethyl-loperamide ([(11)C]dLop), a new P-gp PET radiotracer.
  • To assess the potential of [(11)C]dLop for measuring P-gp function in the rat brain.

Main Methods:

  • [(11)C]dLop was synthesized and radiolabeled.
  • MicroPET brain scans were performed on control rats and rats treated with P-gp inhibitors (cyclosporin A or tariquidar).
  • A one-tissue compartment model estimated radiotracer distribution volume as a measure of P-gp function.

Main Results:

  • [(11)C]dLop showed low brain uptake in control rats.
  • Brain uptake of [(11)C]dLop was significantly higher in rats treated with P-gp inhibitors.
  • Estimated distribution volumes were significantly larger following P-gp inhibition.

Conclusions:

  • The rat brain exhibits increased [(11)C]dLop uptake after P-gp inhibition.
  • [(11)C]dLop is a substrate of P-gp.
  • [(11)C]dLop shows promise as a radiotracer for future P-gp function studies.