Biphasic accumulation kinetics of [99mTc]-hexakis-2- methoxyisobutyl isonitrile in tumour cells and its modulation by lipophilic P-glycoprotein ligands

Teréz Márián, László Balkay, Gábor Szabó, Zoárd T. Krasznai, Zoltán Hernádi, László Galuska, Judit Szabó-Péli, Olga Ésik, Lajos Trón, Zoltán Krasznai

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17 Citations (Scopus)

Abstract

Aim: To study the accumulation and washout kinetics of [ 99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) in MDR positive and MDR negative tumour cells and how this is modified by lipophilic P-glycoprotein ligands. Methods: The tumour cells were incubated in the presence and absence of the ligands and the uptakes of 99mTc- MIBI, rhodamine 123 and 2-[18F]fluoro-2-deoxy-d-glucose ( 18FDG) were measured. Results: The accumulation of 99mTc-MIBI in the tumour cells followed biphasic kinetics. Verapamil and cyclosporin A increased the membrane fluidity and significantly enhanced the 99mTc-MIBI uptake of the MDR negative cells, while the rhodamine 123 uptake was not affected. Verapamil significantly increased the uptake of rhodamine 123 and 18FDG but did not modify that of 99mTc-MIBI in the MDR positive cells. Cyclosporin A significantly increased the 18FDG uptake of the MDR positive and negative tumour cells; these effects were ouabain-sensitive. Depolarization of the cytoplasmic membrane, acidification of the extracellular medium and the administration of CCCP decreased the accumulation of 99mTc-MIBI and rhodamine 123 uptake in the tumour cells. Conclusions: Lipophilic P-glycoprotein ligands modified the biphasic accumulation kinetics of the 99mTc-MIBI uptakes of MDR negative and positive tumour cells in different and complex ways and could therefore mask the P-glycoprotein pump-dependent changes in tracer accumulation.

Original languageEnglish
Pages (from-to)201-209
Number of pages9
JournalEuropean Journal of Pharmaceutical Sciences
Volume25
Issue number2-3
DOIs
Publication statusPublished - Jun 1 2005

Keywords

  • Biphasic Tc-MIBI uptake
  • FDG
  • Lipophilic ligand
  • Multidrug resistance
  • Rhodamine 123

ASJC Scopus subject areas

  • Pharmaceutical Science

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