A comparative study of dynamic contrast‐enhanced MRI parameters as biomarkers for anti‐angiogenic drug therapy
- 23 March 2011
- journal article
- research article
- Published by Wiley in NMR in Biomedicine
- Vol. 24 (9), 1169-1180
- https://doi.org/10.1002/nbm.1680
Abstract
The aim of the present study was to compare three tracer kinetics methods for the analysis of dynamic contrast‐enhanced (DCE) MRI data, namely the generalized kinetics model, the distributed‐parameter model and the initial area under the tumor tracer curve (IAUC) method, in a Phase I study of an anti‐angiogenic drug ABT ‐869; and to explore their utility as biomarkers. Twenty‐eight patients with a range of tumors formed the study population. DCE MRI performed at baseline and 2 weeks post‐treatment was analyzed using all three methods, yielding percentage changes for various tracer kinetics parameters. Correlation analyzes were performed between these parameters and in relation to drug exposure. The association of these parameters with time‐to‐progression was examined using receiver‐operating characteristic and Kaplan–Meier curves. Significant correlation with drug exposure was found for the following parameters: normalized IAUC (IAUCnorm), fractional interstitial volume ve, fractional intravascular volume v1 and permeability PS. However, only ve and PS were effective in predicting late progression. A decrease in ve of more than 1.7% and a decrease in PS of more than 25.1% observed at 2 weeks post‐treatment could be associated with late progression. All three tracer kinetics methods have biomarker potential for assessing the effects of anti‐angiogenic therapy. Copyright © 2011 John Wiley & Sons, Ltd.Keywords
This publication has 24 references indexed in Scilit:
- Computed Tomography Assessment of Cerebral Perfusion Using a Distributed Parameter Tracer Kinetics Model: Validation with H2(15)O Positron Emission Tomography Measurements and Initial Clinical Experience in Patients with Acute StrokeJournal of Cerebral Blood Flow & Metabolism, 2007
- MR in oncology drug developmentNMR in Biomedicine, 2006
- On the Selection of Optimal Flip Angles for$T_1$Mapping of Breast Tumors With Dynamic Contrast-Enhanced Magnetic Resonance ImagingIEEE Transactions on Biomedical Engineering, 2006
- Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitorMolecular Cancer Therapeutics, 2006
- Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PTK787/ZK 222584 Administered Twice Daily in Patients With Advanced CancerJournal of Clinical Oncology, 2005
- Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumoursEuropean Journal Of Cancer, 2005
- Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic TherapyScience, 2005
- Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Biomarker for the Pharmacological Response of PTK787/ZK 222584, an Inhibitor of the Vascular Endothelial Growth Factor Receptor Tyrosine Kinases, in Patients With Advanced Colorectal Cancer and Liver Metastases: Results From Two Phase I StudiesJournal of Clinical Oncology, 2003
- Combretastatin A4 Phosphate Has Tumor Antivascular Activity in Rat and Man as Demonstrated by Dynamic Magnetic Resonance ImagingJournal of Clinical Oncology, 2003
- Measurement of spin-lattice relaxation times with FLASH for dynamic MRI of the breastThe British Journal of Radiology, 1996