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

Anticancer Res. May-Jun 1999;19(3B):2349-53.

Abstract

Background: Our aim was to determine the value of 99mTc-Sestamibi scanning as functional detection method of P-glycoprotein (Pgp) blockade by PSC 833 in solid tumour patients.

Patients and methods: Day 1 and day 4 after 2,200 mg orally administered PSC 833 the tumour area was scanned after intravenous (i.v.) administration of 400 MBq 99mTc-Sestamibi. In tumours with net 99mTc-Sestamibi uptake and in the hepatic region K-efflux was determined. Whole blood was analyzed for 99mTc-Sestamibi, and PSC 833 levels.

Results: Fourteen patients were included. In the only Pgp-positive tumour with positive 99mTc-Sestamibi scanning K-efflux of 99mTc-Sestamibi decreased significantly after PSC 833 intake. A net inhibition of liver efflux of Sestamibi after PSC 833 intake was observed in all evaluable patients. PSC 833 blood levels were all above 2 mg/L during scanning; 99mTc-Sestamibi blood levels post versus pre PSC 833 were unchanged.

Conclusions: PSC 833 induced modulation of K-efflux of 99mTc-Sestamibi in a Pgp positive tumour and in all patients in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Administration, Oral
  • Adult
  • Aged
  • Bone Neoplasms / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Renal Cell / diagnostic imaging
  • Chondrosarcoma / diagnostic imaging
  • Cyclosporins* / administration & dosage
  • Cyclosporins* / pharmacokinetics
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Kidney Neoplasms / diagnostic imaging
  • Lung Neoplasms / diagnostic imaging
  • Male
  • Middle Aged
  • Neoplasms / diagnostic imaging*
  • Neoplasms / metabolism
  • Radionuclide Imaging
  • Radiopharmaceuticals*
  • Sarcoma / diagnostic imaging
  • Technetium Tc 99m Sestamibi*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cyclosporins
  • Radiopharmaceuticals
  • Technetium Tc 99m Sestamibi
  • valspodar