Characterization of P-glycoprotein transport and inhibition in vivo

Eva Barbarics, James F. Kronauge, Dalia Cohen, Alan Davison, Alun G. Jones, James M. Croop

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

The P-glycoprotein is an energy-dependent efflux pump capable of decreasing the intracellular concentration of a broad range of chemotherapeutic agents. [99mTc]Sestamibi, a P-glycoprotein transport substrate, is a sensitive probe of P-glycoprotein function both in vitro and in vivo. A human tumor model in nude mice was evaluated to determine whether [99mTc]Sestamibi could detect in vivo differences in P-glycoprotein expression and P-glycoprotein modulation by the reversal agent SDZ PSC 833. Differential [99mTc]Sestamibi accumulation based upon P-glycoprotein expression was demonstrated in xenografts in vivo. Dose-dependent inhibition of P-glycoprotein function was achieved with SDZ PSC 833. Administration of the reversal agent increased [99mTc]Sestamibi accumulation in the xenografts expressing P-glycoprotein. These observations show that [99mTc]Sestamibi as capable of detecting the modulation of P-glycoprotein in a solid tumor model by the reversal agent SDZ PSC 833.

Original languageEnglish (US)
Pages (from-to)276-282
Number of pages7
JournalCancer Research
Volume58
Issue number2
StatePublished - Jan 15 1998

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Barbarics, E., Kronauge, J. F., Cohen, D., Davison, A., Jones, A. G., & Croop, J. M. (1998). Characterization of P-glycoprotein transport and inhibition in vivo. Cancer Research, 58(2), 276-282.