Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging
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Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here.
• Tumour vascular function is key to tumour development and treatment
• Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascular function
• Thus DCE-MRI with pharmacokinetic models can assess novel treatments
• Many recent developments are advancing the accuracy of and information from DCE-MRI
• Establishing common methodology across multiple centres is challenging and requires accepted guidelines
KeywordsDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) Tumour vasculature Angiogenesis Cancer Early phase trials
We are grateful for comments received from Y. Hwang, E. Jackson, R. Sims, J. Evelhoch, M. Silva, W. Vennart, M. Clemence, B. Kiefer, and M. Rosen. We would also like to acknowledge the Experimental Cancer Medicine Centre (ECMC) Imaging Steering Committee (M. Leach, E. Aboagye, F. Gilbert, V. Goh, A. Jackson, D. Lomas, B. Morgan, and R. Plummer) and the ECMC Secretariat for supporting the workshop on tumour vascularity in May 2010 and coordinating activities, and all of the speakers and delegates who contributed to the meeting. The Experimental Cancer Medicine Centre Initiative is jointly funded by Cancer Research UK, the National Institute for Health Research in England, and the Departments of Health for Scotland, Wales, and Northern Ireland.
Conflict of Interest
M.O. Leach and D.J. Collins: Software developed at the Institute of Cancer Research and using some of the approaches referred to in this paper may be commercialised by the Institute of Cancer Research and commercialised or licensed to users. In those cases employees may receive some income under the Institute's rewards to inventors scheme.
B. Whitcher: Employed by GlaxoSmithKline (pharmaceutical industry) at the time of the ECMC workshop and until 6 May 2011. Now employed by Mango Solutions (software industry) and provides medical image analysis services to the pharmaceutical industry.
G. Parker: Received research grant income and consultancy income from pharmaceutical companies for work in DCE-MRI associated with clinical trials. Specifically, within the last year received research grant income from AstraZeneca, Pfiizer, GSK, Roche, Genentech, Bayer, and Merck-Serono. Received consultancy income from Bayer. Also a shareholder and director of Bioxydyn limited, a specialist imaging company with an interest in DCE-MRI.
G. Karczmar: Research has been supported by Philips Medical Systems and Bayer.
A. Padhani: Consultancy work for IXICO and Roche. DCE trial work with Roche and Oxigene.
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