Evaluation of MS-209, a novel multidrug-resistance-reversing agent, in tumour-bearing mice by technetium-99m-MIBI imaging.
MS-209 is a newly synthesised multidrug-resistance (MDR)-reversing agent with few side-effects. In this study, we evaluated the effect of MS-209 on P-glycoprotein (Pgp)-positive tumours in mice by means of technetium-99m methoxyisobutylisonitrile (MIBI) imaging. Mice received Pgp-negative KB-3-1 or Pgp-positive KB-C1 cell xenografts. KB-3-1-bearing mice were administered 0 or 100 mg/kg of MS-209 (groups S0 and S100, respectively), and KB-C1-bearing mice 0, 50, 100 or 200 mg/kg (groups R0, R50, R100 and R200, respectively), 30 min before imaging studies. Dynamic 99mTc-MIBI images were acquired for 30 min, followed by biodistribution studies. Washout of 99mTc-MIBI from the tumours was faster in group R0 than in group S0 on visual analysis, and the washout half-time estimated by region of interest analysis was shorter in group R0 than in group S0. Biodistribution studies revealed that 99mTc-MIBI accumulation in tumours (expressed as %ID/g) was also lower in group R0 than in group S0. MS-209 delayed the 99mTc-MIBI washout from KB-C1 tumours. Washout half-time was longer in groups R50, R100 and R200 than in group R0. A higher %ID/g was observed in groups R100 and R200 than in group R0. In KB-3-1 tumours, MS-209 had no effect on the washout half-time or the %ID/g. This study demonstrated that MS-209 increases the 99mTc-MIBI accumulation in Pgp-positive tumours. The MDR-reversing effect of MS-209 could be effectively evaluated with 99mTc-MIBI visually and non-invasively in vivo. 99mTc-MIBI imaging with MS-209 prior to chemotherapy should contribute significantly to the treatment strategy in patients with multidrug-resistant tumours.
Tatsumi
Mitsuaki
M
Division of Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Japan. tatsumi@tracer.med.osaka-u.ac.jp
Tsuruo
Takashi
T
Nishimura
Tsunehiko
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D019450:Genes, MDR / Q000235:genetics; D006801:Humans; D007624:KB Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011804:Quinolines / Q000008:administration & dosage* / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011804:Quinolines; D019275:Radiopharmaceuticals; C087719:dofequidar; D017256:Technetium Tc 99m Sestamibi