Imaging multidrug resistance P-glycoprotein transport function using microPET with technetium-94m-sestamibi

Mol Imaging. 2005 Jan-Mar;4(1):30-9. doi: 10.1162/15353500200504166.

Abstract

The best characterized mechanism of multidrug resistance (MDR) in cancer involves the MDR1 efflux transporter P-glycoprotein (Pgp). The positron-emitting radiotracer hexakis(2-methoxyisobutylisonitrile)-(94m)Tc ((94m)Tc-MIBI) was synthesized and validated in cell transport studies as a substrate for MDR1 Pgp. In vivo small-scale PET imaging and biodistribution studies of mdr1a/1b (-/-) gene deleted and wild-type mice demonstrated the use of (94m)Tc-MIBI to detect Pgp function. The reversal effect of a Pgp modulator was shown in tissue distribution studies of KB 3-1 (Pgp-) and KB 8-5 (Pgp+) tumor-bearing nude mice. The current (94m)Tc-MIBI experiments parallel previous studies employing (99m)Tc-MIBI, showing essentially identical performance of the two technetium radiotracers and providing biological validation of (94m)Tc-MIBI for PET imaging of multidrug resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Dibenzocycloheptenes / pharmacology
  • Drug Resistance, Multiple
  • Humans
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Positron-Emission Tomography / methods*
  • Protein Transport
  • Quinolines / pharmacology
  • Radiopharmaceuticals / analysis*
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Substrate Specificity
  • Technetium Tc 99m Sestamibi / analysis*
  • Technetium Tc 99m Sestamibi / pharmacokinetics
  • Tissue Distribution
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Dibenzocycloheptenes
  • Quinolines
  • Radiopharmaceuticals
  • zosuquidar trihydrochloride
  • Technetium Tc 99m Sestamibi