Journal of Cellular Biochemistry

Synergy between anti-CCL2 and docetaxel as determined by DW-MRI in a metastatic bone cancer model

Authors

  • Stefan Rozel,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven, University of Technology, Eindhoven, The Netherlands
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  • Craig J. Galbán,

    1. Departments of Radiology and Radiation Oncology, Center for Molecular Imaging, University of Michigan, Ann Arbor, Michigan 48109-2200
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  • Klaas Nicolay,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven, University of Technology, Eindhoven, The Netherlands
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  • Kuei C. Lee,

    1. Departments of Radiology and Radiation Oncology, Center for Molecular Imaging, University of Michigan, Ann Arbor, Michigan 48109-2200
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  • Sudha Sud,

    1. Departments of Internal Medicine and Urology, University of Michigan Comprehensive Cancer Center, Michigan Center for Translational Pathology, Ann Arbor, Michigan 48109
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  • Chris Neeley,

    1. Departments of Internal Medicine and Urology, University of Michigan Comprehensive Cancer Center, Michigan Center for Translational Pathology, Ann Arbor, Michigan 48109
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  • Linda A. Snyder,

    1. Ortho Biotech Oncology Research and Development, Centocor, 145 King of Prussia Road, Radnor, Pennsylvania 19087
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  • Thomas L. Chenevert,

    1. Departments of Radiology and Radiation Oncology, Center for Molecular Imaging, University of Michigan, Ann Arbor, Michigan 48109-2200
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  • Alnawaz Rehemtulla,

    1. Departments of Radiology and Radiation Oncology, Center for Molecular Imaging, University of Michigan, Ann Arbor, Michigan 48109-2200
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  • Brian D. Ross,

    1. Departments of Radiology and Radiation Oncology, Center for Molecular Imaging, University of Michigan, Ann Arbor, Michigan 48109-2200
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  • Kenneth J. Pienta

    Corresponding author
    1. Departments of Internal Medicine and Urology, University of Michigan Comprehensive Cancer Center, Michigan Center for Translational Pathology, Ann Arbor, Michigan 48109
    • 7308 CCC, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5946.
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Abstract

Metastatic prostate cancer continues to be the second leading cause of cancer death in American men with an estimated 28,660 deaths in 2008. Recently, monocyte chemoattractant protein-1 (MCP-1, CCL2) has been identified as an important factor in the regulation of prostate metastasis. CCL2, shown to attract macrophages to the tumor site, has a direct promotional effect on tumor cell proliferation, migration, and survival. Previous studies have shown that anti-CCL2 antibodies given in combination with docetaxel were able to induce tumor regression in a pre-clinical prostate cancer model. A limitation for evaluating new treatments for metastatic prostate cancer to bone is the inability of imaging to objectively assess response to treatment. Diffusion-weighted MRI (DW-MRI) assesses response to anticancer therapies by quantifying the random (i.e., Brownian) motion of water molecules within the tumor mass, thus identifying cells undergoing apoptosis. We sought to measure the treatment response of prostate cancer in an osseous site to docetaxel, an anti-CCL2 agent, and combination treatments using DW-MRI. Measurements of tumor apparent diffusion coefficient (ADC) values were accomplished over time during a 14-day treatment period and compared to response as measured by bioluminescence imaging and survival studies. The diffusion data provided early predictive evidence of the most effective therapy, with survival data results correlating with the DW-MRI findings. DW-MRI is under active investigation in the pre-clinical and clinical settings to provide a sensitive and quantifiable means for early assessment of cancer treatment outcome. J. Cell. Biochem. 107: 58–64, 2009. © 2009 Wiley-Liss, Inc.

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