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Eur J Nucl Med Mol Imaging. 2002 Mar;29(3):288-94.

Evaluation of MS-209, a novel multidrug-resistance-reversing agent, in tumour-bearing mice by technetium-99m-MIBI imaging.

Author information

1
Division of Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Japan. tatsumi@tracer.med.osaka-u.ac.jp

Abstract

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.

PMID:
12002701
[Indexed for MEDLINE]

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