19F NMR in vivo spectroscopy reflects the effectiveness of perfusion-enhancing vascular modifiers for improving gemcitabine chemotherapy
✍ Scribed by Greg O. Cron; Nelson Beghein; Réginald Ansiaux; Philippe Martinive; Olivier Feron; Bernard Gallez
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 615 KB
- Volume
- 59
- Category
- Article
- ISSN
- 0740-3194
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✦ Synopsis
Abstract
Nuclear magnetic resonance spectroscopy of fluorine‐19 (^19^F NMR) has proven useful for evaluating kinetics of fluorinated chemotherapy drugs in tumors in vivo. This work investigated how three perfusion‐enhancing vascular modifiers (BQ123, thalidomide, and Botulinum neurotoxin type A [BoNT‐A]) would affect the chemotherapeutic efficacy of gemcitabine, a fluorinated drug widely used in human cancer treatment. Murine tumor growth experiments demonstrated that only BoNT‐A showed a strong trend to enhance tumor growth inhibition by gemcitabine (1.7 days growth delay, P = 0.052, Student t‐test). In accord with these results, ^19^F NMR experiments showed that only BoNT‐A increased significantly the uptake of gemcitabine in tumors (50% increase, P = 0.0008, Student t‐test). Further experiments on gemcitabine kinetics (NMR vs time) and distribution (^19^F MRI) confirmed the uptake‐enhancing properties of BoNT‐A. The results of this study demonstrate that ^19^F NMR can monitor modulation of the pharmacokinetics of fluorinated chemotherapy drugs in tumors. The results also show that ^19^F NMR data can give a strong indication of the effectiveness of perfusion‐enhancing vascular modifiers for improving gemcitabine chemotherapy in murine tumors. ^19^F NMR is a promising tool for preclinical evaluation of such vascular modifiers and may ultimately be used in the clinic to monitor how these modifiers affect chemotherapy. Magn Reson Med, 2007. © 2007 Wiley‐Liss, Inc.