Effect of Tamoxifen in an Experimental Model of Breast Tumor Studied by Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Different Contrast Agents

Objectives:The aim of this study was to compare the efficacy of gadoteridol, B22956/1 (a new protein binding blood pool contrast agent), and (Gd-DTPA)37-albumin in detecting, by dynamic contrast-enhanced magnetic resonance imaging (MRI), the effect in vivo of tamoxifen in an experimental model of breast tumor implanted in rats. Materials and Methods:Tumors were induced by subcutaneous injection of 106 mammary adenocarcinoma cells (13762 MAT B III). Treatment with tamoxifen (or vehicle) started on day 4 after implantation. On day 10 after implantation, animals were observed by MRI using B22956/1 (or gadoteridol) and, 24 hours later, using (Gd-DTPA)37–albumin. Results:Dynamic contrast-enhanced magnetic resonance imaging data showed that tamoxifen treatment decreased vascular permeability to B22956/1, whereas no difference was detectable in permeability to gadoteridol or to (Gd-DTPA)37–albumin. No effect on fractional plasma volume was detected with either of contrast agents. Conclusions:B22956/1 is superior to both small Gd chelates and macromolecular contrast agents in the assessment of the effect of tamoxifen treatment on tumor vasculature.

[1]  M. Brechbiel,et al.  Identifying Tumor Vascular Permeability Heterogeneity With Magnetic Resonance Imaging Contrast Agents , 2002, Investigative radiology.

[2]  R. Brasch,et al.  Tumor microvascular changes to anti-angiogenic treatment assessed by MR contrast media of different molecular weights. , 2002, Academic radiology.

[3]  K. Brindle,et al.  Differential sensitivity of two adenocarcinoma xenografts to the anti‐vascular drugs combretastatin A4 phosphate and 5,6‐dimethylxanthenone‐4‐acetic acid, assessed using MRI and MRS , 2002, NMR in biomedicine.

[4]  M. Knopp,et al.  Functional tumor imaging with dynamic contrast‐enhanced magnetic resonance imaging , 2003, Journal of magnetic resonance imaging : JMRI.

[5]  K. Scheffler,et al.  B22956/1, a new intravascular contrast agent for MRI: first administration to humans--preliminary results. , 2002, Academic radiology.

[6]  Thomas M. Link,et al.  Correlation of dynamic contrast-enhanced magnetic resonance imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media , 1998, Pediatric Radiology.

[7]  A. Mazar,et al.  An antiangiogenic urokinase-derived peptide combined with tamoxifen decreases tumor growth and metastasis in a syngeneic model of breast cancer. , 2002, Cancer research.

[8]  Viktor Novikov,et al.  Tumor microvascular changes in antiangiogenic treatment: Assessment by magnetic resonance contrast media of different molecular weights , 2004, Journal of magnetic resonance imaging : JMRI.

[9]  R. Brasch,et al.  MRI monitoring of Avastin™ antiangiogenesis therapy using B22956/1, a new blood pool contrast agent, in an experimental model of human cancer , 2004, Journal of magnetic resonance imaging : JMRI.

[10]  D Matthaei,et al.  Inversion recovery snapshot FLASH MR imaging. , 1989, Journal of computer assisted tomography.

[11]  Robyn L. Birdwell,et al.  Magnetic Resonance Imaging Characteristics of Fibrocystic Change of the Breast , 2005, Investigative radiology.

[12]  K. Bae,et al.  Evaluation of 1H-Magnetic Resonance Spectroscopy of Breast Cancer Pre- and Postgadolinium Administration , 2005, Investigative radiology.

[13]  Jurgen J Fütterer,et al.  Variability in the Description of Morphologic and Contrast Enhancement Characteristics of Breast Lesions onMagnetic Resonance Imaging , 2005, Investigative radiology.

[14]  P. Anelli,et al.  Preclinical profile and clinical potential of gadocoletic acid trisodium salt (B22956/1), a new intravascular contrast medium for MRI. , 2002, Academic radiology.

[15]  Andrea Sbarbati,et al.  In Vivo Assessment of Antiangiogenic Activity of SU6668 in an Experimental Colon Carcinoma Model , 2004, Clinical Cancer Research.

[16]  C. de Haën,et al.  Coupling of DTPA to proteins: a critical analysis of the cyclic dianhydride method in the case of insulin modification. , 1992, Bioconjugate chemistry.

[17]  P. Anelli,et al.  In vitro and in vivo hepatic transport of the magnetic resonance imaging contrast agent B22956/1: role of MRP proteins. , 2002, Biochemical and biophysical research communications.

[18]  G. Hortobagyi,et al.  Angiogenesis modulation in cancer research: novel clinical approaches , 2002, Nature Reviews Drug Discovery.

[19]  D M Shames,et al.  Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: A quantitative noninvasive technique , 1993, Magnetic resonance in medicine.

[20]  E. Uzgiris.  The Role of Molecular Conformation on Tumor Uptake of Polymeric Contrast Agents , 2004, Investigative radiology.

[21]  R Weissleder,et al.  Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging. , 2001, Bioconjugate chemistry.

[22]  Carlo Catalano,et al.  Color-Coded Automated Signal Intensity Curves for Detection and Characterization of Breast Lesions: Preliminary Evaluation of a New Software Package for Integrated Magnetic Resonance-Based Breast Imaging , 2005, Investigative radiology.

[23]  A R Padhani,et al.  In vivo monitoring of tumor angiogenesis with MR imaging. , 2000, Academic radiology.

[24]  M. Dewhirst,et al.  Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[25]  Joachim Boettcher,et al.  Further Signs in the Evaluation of Magnetic Resonance Mammography: A Retrospective Study , 2005, Investigative radiology.

[26]  J L Evelhoch,et al.  Key factors in the acquisition of contrast kinetic data for oncology , 1999, Journal of magnetic resonance imaging : JMRI.

[27]  Robert C. Brasch,et al.  MRI monitoring of tumor response following angiogenesis inhibition in an experimental human breast cancer model , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[28]  Viktor Novikov,et al.  The Choice of Region of Interest Measures in Contrast-Enhanced Magnetic Resonance Image Characterization of Experimental Breast Tumors , 2005, Investigative radiology.

[29]  Stefan Delorme,et al.  Classification of Signal-Time Curves Obtained by Dynamic Magnetic Resonance Mammography: Statistical Comparison of Quantitative Methods , 2005, Investigative radiology.

[30]  B. Vojnovic,et al.  Evaluation of the anti‐vascular effects of combretastatin in rodent tumours by dynamic contrast enhanced MRI , 2002, NMR in biomedicine.

[31]  A. Padhani.  Dynamic contrast‐enhanced MRI in clinical oncology: Current status and future directions , 2002, Journal of magnetic resonance imaging : JMRI.