19F NMR In Vivo Spectroscopy Reflects the Effectiveness of Perfusion-Enhancing Vascular Modifiers for Improving

Nuclear magnetic resonance spectroscopy of fluorine-19 (19F 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, tha-lidomide, and Botulinum neurotoxin type A [BoNT-A]) would affect the chemotherapeutic efficacy of gemcitabine, a fluori-nated 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, 19F 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 distri-bution (19F MRI) confirmed the uptake-enhancing properties of BoNT-A. The results of this study demonstrate that 19F NMR can monitor modulation of the pharmacokinetics of fluorinated che-motherapy drugs in tumors. The results also show that 19F NMR data can give a strong indication of the effectiveness of perfu-sion-enhancing vascular modifiers for improving gemcitabine chemotherapy in murine tumors. 19F NMR is a promising tool for preclinical evaluation of such vascular modifiers and may ulti-mately be used in the clinic to monitor how these modifiers affect chemotherapy. Magn Reson Med 59:19–27, 2008