99mTc-Sestamibi scanning with SDZ PSC 833 as a functional detection method for resistance modulation in patients with

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Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease
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M Bakker1, W T van der Graaf, D A Piers

  • 1Department of Pulmonary Disease, University Hospital Groningen, The Netherlands.

Anticancer Research
|September 3, 1999
PubMed
Abstract

Insights

99mTc-Sestamibi scanning effectively detects P-glycoprotein (Pgp) blockade by PSC 833 in solid tumors. PSC 833 modulated K-efflux in Pgp-positive tumors and liver, indicating functional Pgp inhibition.

Area of Science:

  • Nuclear medicine
  • Pharmacology
  • Oncology

Background:

  • 99mTc-Sestamibi scanning is a functional detection method.
  • P-glycoprotein (Pgp) is a key factor in multidrug resistance.
  • PSC 833 is a Pgp inhibitor.

Purpose of the Study:

  • To evaluate 99mTc-Sestamibi scanning for detecting Pgp blockade by PSC 833.
  • To assess the functional impact of PSC 833 on Pgp activity in solid tumors.

Main Methods:

  • 14 solid tumor patients received oral PSC 833 (2,200 mg).
  • 99mTc-Sestamibi (400 MBq i.v.) was administered on days 1 and 4.
  • Tumor and liver K-efflux, and blood levels of 99mTc-Sestamibi and PSC 833 were analyzed.

Main Results:

  • One Pgp-positive tumor showed decreased 99mTc-Sestamibi K-efflux post-PSC 833.
  • Liver efflux of Sestamibi was inhibited in all evaluable patients.
  • PSC 833 blood levels remained >2 mg/L; 99mTc-Sestamibi levels were unchanged.

Conclusions:

  • PSC 833 modulated 99mTc-Sestamibi K-efflux in a Pgp-positive tumor.
  • PSC 833 demonstrated functional Pgp inhibition in the liver of all patients.

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