1: Magn Reson Med. 2008 Jan;59(1):19-27.

(19)F NMR in vivo spectroscopy reflects the effectiveness of perfusion-enhancing 
vascular modifiers for improving gemcitabine chemotherapy.

Cron GO, Beghein N, Ansiaux R, Martinive P, Feron O, Gallez B.

Laboratory of Biomedical Magnetic Resonance and Laboratory of Medicinal Chemistry
and Radiopharmacy, Université Catholique de Louvain, UCL, Brussels, Belgium.

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. (c) 2007 Wiley-Liss, Inc.

PMID: 18050344 [PubMed - in process]

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