Dynamic contrast-enhanced MRI in clinical trials of antivascular therapies.
AffiliationImaging, Genomics and Proteomics Research Group, School of Cancer and Enabling Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK. james.o'connor@ manchester.ac.uk
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AbstractAbout 100 early-phase clinical trials and investigator-led studies of targeted antivascular therapies--both anti-angiogenic and vascular-targeting agents--have reported data derived from T1-weighted dynamic contrast-enhanced (DCE)-MRI. However, the role of DCE-MRI for decision making during the drug-development process remains controversial. Despite well-documented guidelines on image acquisition and analysis, several key questions concerning the role of this technique in early-phase trial design remain unanswered. This Review describes studies of single-agent antivascular therapies, in which DCE-MRI parameters are incorporated as pharmacodynamic biomarkers. We discuss whether these parameters, such as volume transfer constant (K(trans)), are reproducible and reliable biomarkers of both drug efficacy and proof of concept, and whether they assist in dose selection and drug scheduling for subsequent phase II trials. Emerging evidence indicates that multiparametric analysis of DCE-MRI data offers greater insight into the mechanism of drug action than studies measuring a single parameter, such as K(trans). We also provide an overview of current data and appraise the future directions of this technique in oncology trials. Finally, major hurdles in imaging biomarker development, validation and qualification that hinder a wide application of DCE-MRI techniques in clinical trials are addressed.
CitationDynamic contrast-enhanced MRI in clinical trials of antivascular therapies. 2012, 9 (3):167-77 Nat Rev Clin Oncol
JournalNature Reviews Clinical Oncology
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