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Dynamic Contrast Enhanced Magnetic Resonance Imaging of an Orthotopic Pancreatic Cancer Mouse Model
Published on: April 18, 2015
Antivascular cancer treatments: functional assessments by dynamic contrast-enhanced magnetic resonance imaging
1Paul Strickland Scanner Centre, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, United Kingdom. anwar.padhani@paulstrickland-scannercentre.org.uk
Abstract:
New anticancer therapeutics that target tumor blood vessels promise improved efficacy and tolerability in humans. Early phase 1 drug trials have shown that the maximum tolerated dose may be inappropriate for more advanced clinical studies with efficacy endpoints. More advanced clinical trials have demonstrated that morphologic assessments of tumor response are of limited value for gauging the efficacy of treatment. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can serve as pharmacodynamic indicator of biological activity for antivascular cancer drugs by helping to define the biologically active dose. DCE-MRI studies may also predict the efficacy of treatment on the basis of changes observed. If DCE-MRI is to be used for the selection of antivascular drugs that advance into efficacy trials, then it will be necessary to develop standardized approaches to measurement and robust analytic approaches with clear accepted endpoints specified prospectively that have biological validity. Such developments will be essential for multicenter trials in which it will be necessary to establish effective cross-site standardization of measurements and evaluation.
Insights
Dynamic contrast-enhanced MRI (DCE-MRI) can assess antivascular cancer drug activity and predict treatment efficacy. Standardized DCE-MRI methods are crucial for reliable multicenter trials and selecting drugs for further development.
Area of Science:
- Oncology
- Radiology
- Pharmacology
Background:
- Novel anticancer therapeutics targeting tumor vasculature offer potential for enhanced efficacy and patient tolerability.
- Traditional assessments like maximum tolerated dose and morphological tumor response lack predictive value in advanced clinical trials for antivascular agents.
Purpose of the Study:
- To highlight the utility of Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) as a pharmacodynamic tool for antivascular cancer drugs.
- To emphasize the need for standardized DCE-MRI methodologies and robust analytical approaches for reliable clinical trial endpoints.
Main Methods:
- Utilizing DCE-MRI to measure biological activity and predict treatment efficacy of antivascular cancer drugs.
- Evaluating the limitations of morphological assessments in advanced clinical studies.
Main Results:
- DCE-MRI can serve as a pharmacodynamic indicator, defining the biologically active dose of antivascular drugs.
- Observed changes in DCE-MRI may predict treatment efficacy, offering a more sensitive endpoint than morphological assessments.
Conclusions:
- Standardized DCE-MRI measurement and analysis are essential for selecting antivascular drugs for efficacy trials.
- Development of robust, prospectively defined endpoints with biological validity is critical for multicenter trials and cross-site standardization.
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