Imaging, 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
Nat Rev Clin Oncol. 2012 Feb 14;9(3):167-77. doi: 10.1038/nrclinonc.2012.2.
About 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.
约 100 项靶向抗血管治疗的早期临床研究和研究者主导的研究——包括抗血管生成和血管靶向药物——已经报告了来自 T1 加权动态对比增强（DCE）MRI 的数据。然而，DCE-MRI 在药物开发过程中的决策中的作用仍然存在争议。尽管有关于图像采集和分析的详细指南，但在早期试验设计中，该技术的作用仍存在几个关键问题尚未得到解答。本综述描述了单药抗血管治疗的研究，其中 DCE-MRI 参数被作为药效学生物标志物纳入。我们讨论了这些参数，如容积转移常数（K(trans)），是否是药物疗效和概念验证的重现性和可靠的生物标志物，以及它们是否有助于选择后续 II 期试验的剂量和药物方案。新出现的证据表明，DCE-MRI 数据的多参数分析比测量单个参数（如 K(trans)）的研究更能深入了解药物作用的机制。我们还概述了当前的数据，并评估了该技术在肿瘤学试验中的未来方向。最后，讨论了成像生物标志物开发、验证和鉴定中的主要障碍，这些障碍阻碍了 DCE-MRI 技术在临床试验中的广泛应用。
