Dynamic contrast-enhanced MRI in oncology drug development.
Angiogenesis, long recognized as a key factor in tumor growth and metastasis, has been the target of new anticancer treatment paradigms. Development of antiangiogenesis drugs is challenging, mainly due to the difficulty of determining the correct dosage and the time required to observe a clinical effect. In the past decade, imaging has shown potential to answer these questions and accelerate the drug development process by providing functional, morphological, and even molecular characterization. In this review, we describe existing challenges to modern drug development and the potential of imaging biomarkers to monitor drug bioactivity and establish early response of drug efficacy. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), particularly attractive for its non-invasiveness and high spatial resolution, has been useful for measuring properties of tumor microvasculature. The general methodology of DCE-MRI is described, in addition to measurable hemodynamic parameters compared to other imaging modalities. Experience with DCE-MRI in antiangiogenesis cancer therapy and results from correlative studies are examined. Current challenges for DCE-MRI, especially in relation to the required sensitivity and reproducibility, are highlighted. We conclude with an outlook on the future of DCE-MRI, including its role in the emerging field of imaging molecular markers of angiogenesis for target-specific therapy.
Cheng
Hai-Ling Margaret
HL
Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada. hai-ling.cheng@sickkids.ca
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000517:prevention & control*; D012039:Regional Blood Flow / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents