Improved assessment of tumour angiogenesis with DCE–MRI

Abstract

Introduction: Tumour angiogenesis is a major hallmark of cancer. Current methods include dynamic contrast-enhancement magnetic resonance imaging (DCE– MRI), which can measure vascular permeability; a biomarker of angiogenesis. We have developed a new method that compares the pharmacokinetic uptake and washout of a contrast agent in tumour tissue and muscle tissue, known as the reference region model (RRM). The method uses a ratio of the pharmacokinetics in both tissues to eliminate physiological effects other than vascular permeability from the evaluation. Objectives: Determine whether the change in angiogenesis can be used to monitor early response to antiangiogenic chemotherapies by measuring vascular permeability with DCE– MRI Materials and methods: SCID mice were injected subcutaneously with MDA-MB-231 breast tumours. Each mouse was anesthetized with isoflurane gas. MRI was used to take five images of the mouse. After the fifth scan, 50μl of 20mg/ml gadopentetate dimeglumine (Magnevist®, Bayer Schering Pharma, Berlin, Germany) was administered intravenously into a catheter inserted in the mouse tail vain. A total of 60 images were taken over 32 minutes. The study was repeated with 50μl of 20mg/ml benuryl (Probenecid®, Sigma Aldrich, St Louis, MO, USA). Results: Benuryl increased tumour uptake and decreased renal uptake and was more effective with gadopentetate dimeglumine than gadodiamide (Omniscan™ , GE Healthcare, Little Chalfont, UK). The new methods to improve sensitivity and specificity of DCE– MRI are pictorial representation of the new reference agent model for DCE– MRI and the difference in perfusion between the tumour and normal tissue. Conclusions: RRM is a good example of assessing the angiogenesis of the tumour without invading it. Benuryl decreases renal uptake and increases tumour uptake of gadopentetate dimeglumine but was less effective with gadodiamide These data suggest that gadopentetate dimeglumine will improve the measurement of the tumour angiogenesis. Acknowledgements: This work was supported by the University of Arizona Cancer Center and the National Cancer Institute. A Alabdulqader, F Alangari, and G Niaz were supported by the summer training programme by Al-Imam University. L Chen is supported by a Technology and Research Initiative Fund Imaging Fellowship from the state of Arizona.