Use of dynamic contrast-enhanced MRI to evaluate acute treatment with ZD6474, a VEGF signalling inhibitor, in PC-3 prostate tumours

D. Checkley, J. J. Tessier, J. Kendrew, J. C. Waterton, S. R. Wedge

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), using gadopentetate dimeglumine, was used to monitor acute effects on tumour vascular permeability following inhibition of vascular endothelial growth factor-A (VEGF-A) signal transduction. Mice bearing PC-3 human prostate adenocarcinoma xenografts were treated with ZD6474, a VEGF receptor-2 (KDR) tyrosine kinase inhibitor, The pharmacokinetic parameter Ktrans was obtained, which reflects vascular permeability and perfusion. Mice were imaged immediately before, and following, acute treatment with ZD6474 (12.5-100 mg kg-1 orally). Whole tumours were analysed to obtain mean Ktrans values, and a histogram approach was used to examine intratumour heterogeneity. Reproducibility of Ktrans measurements gave inter- and intra-animal coefficients of variation of 40 and 18%, respectively. Dose-related reductions in Ktrans were evident following acute ZD6474 treatment A K trans reduction of approximately 30% (P
    Original languageEnglish
    Pages (from-to)1889-1895
    Number of pages6
    JournalBritish Journal of Cancer
    Volume89
    Issue number10
    DOIs
    Publication statusPublished - 17 Nov 2003

    Keywords

    • DCE-MRI
    • Gadopentetate dimeglumine
    • Tyrosine kinase inhibitor
    • Vascular permeability
    • VEGF
    • ZD6474

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