Title: Pre-clinical assessment of anti-vascular drugs using quantitative dynamic contrast-enhanced MRI

Authors: Inna V. Linnik; Steve R. Williams; Karen E. Davies; Alan T. McGown; John A. Hadfield; David L. Buckley

Addresses: Imaging Proteomics and Genomics Research Group, Manchester Academic Health Sciences Centre University of Manchester, Oxford Road, Manchester, M13 9PT, UK. ' Imaging Proteomics and Genomics Research Group, Manchester Academic Health Sciences Centre University of Manchester, Oxford Road, Manchester, M13 9PT, UK. ' Imaging Proteomics and Genomics Research Group, Manchester Academic Health Sciences Centre University of Manchester, Oxford Road, Manchester, M13 9PT, UK. ' Centre for Molecular Drug Design, Kidscan Laboratories, Cockcroft Building, University of Salford, Manchester, M5 4WT, UK. ' Centre for Molecular Drug Design, Kidscan Laboratories, Cockcroft Building, University of Salford, Manchester, M5 4WT, UK. ' Division of Medical Physics, University of Leeds, Room 10.63, Level 10 Worsley Building, Clarendon Way, Leeds LS2 9JT, West Yorks, UK

Abstract: The effect of novel anti-cancer agents on the vascular properties of radiation-induced fibrosarcomas in C3H-strain mice was evaluated in vivo using dynamic contrast-enhanced (DCE) MRI. A T₁-weighted volume acquisition was used to obtain DCE-MRI data. Pre-contrast T₁ measurements and the contrast agent arterial input function were used to estimate the volume transfer constant (K^trans) and extravascular extracellular volume fraction (v_e). Five novel combretastatin analogues, combretastatin A-4 (CA-4) and hazelnut oil (vehicle) were tested for their effect 24 hours after administration on the tumours. Three of the five agents and the positive control (CA-4), significantly decreased tumour K^trans and v_e: K^trans for CA-4 by 72%; fluorocombretastatin by 75%; methylcombretastatin by 68%; and ve by 40% for methylcombretastatin and 75% for the combretastatin quinone. These agents were recommended for further consideration. These results suggest that DCE-MRI may be a useful tool for pre-clinical evaluation of anti-cancer drugs.

Keywords: anti-cancer agents; dynamic contrast-enhanced MRI; tumour modelling; radiation induced fibrosarcoma; anti-vascular drugs; magnetic resonance imaging; pre-clinical evaluation; drug evaluation; cancer drugs.

DOI: 10.1504/IJMEI.2012.050277

International Journal of Medical Engineering and Informatics, 2012 Vol.4 No.4, pp.362 - 372

Published online: 11 Aug 2014 *

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