Detection of targeted perfluorocarbon nanoparticle binding using 19F diffusion weighted MR spectroscopy

Authors

  • Emily A. Waters,

    1. Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, Missouri
    2. Department of Biomedical Engineering, Washington University, St. Louis, Missouri
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    • Drs. Waters and Chen contributed equally to this work.

  • Junjie Chen,

    1. Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, Missouri
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    • Drs. Waters and Chen contributed equally to this work.

  • Xiaoxia Yang,

    1. Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, Missouri
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  • Huiying Zhang,

    1. Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, Missouri
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  • Robert Neumann,

    1. Department of Surgery, Division of Urology, Washington University Medical School, St. Louis, Missouri
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  • Andrea Santeford,

    1. Department of Surgery, Division of Urology, Washington University Medical School, St. Louis, Missouri
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  • Jeffrey Arbeit,

    1. Department of Surgery, Division of Urology, Washington University Medical School, St. Louis, Missouri
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  • Gregory M. Lanza,

    1. Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, Missouri
    2. Department of Biomedical Engineering, Washington University, St. Louis, Missouri
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  • Samuel A. Wickline

    Corresponding author
    1. Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, Missouri
    2. Department of Biomedical Engineering, Washington University, St. Louis, Missouri
    • C-TRAIN group, Campus Box 8215, Cortex Building, Suite 101, 4320 Forest Park Avenue, St. Louis, MO 63108
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Abstract

Real-time detection of targeted contrast agent binding is challenging due to background signal from unbound agent. 19F diffusion weighted MR spectroscopy (DWS) could selectively detect binding of angiogenesis-targeted perfluorocarbon nanoparticles in vivo. Transgenic K14-HPV16 mice with epidermal squamous carcinomas exhibiting up-regulated neovasculature were used, with nontransgenic littermates as controls. Mice were treated with αvβ3-integrin targeted perfluorocarbon nanoparticles. 19F DWS (b-values from 0 to 16,000 s/mm2) was performed on mouse ears in vivo at 11.74 Tesla. Progressive decay of 19F signal with increased diffusion weighting at low b-values (< 1500 s/mm2) was observed in ears of both K14-HPV16 and control mice, demonstrating suppression of background 19F signal from unbound nanoparticles in the blood. Much of the 19F signal from ears of K14-HPV16 mice persisted at high b-values, indicating a stationary signal source, reflecting abundant nanoparticle binding to angiogenesis. 19F signal in controls decayed completely at high b-values (> 1500 s/mm2), reflecting a moving signal source due to absence of angiogenesis (no binding sites). Estimated ADCs of nanoparticles in K14-HPV16 and control mice were 33.1 ± 12.9 μm2/s and 19563 ± 5858 μm2/s (p < 0.01). In vivo 19F DWS can be used for specific detection of bound perfluorocarbon nanoparticles by selectively suppressing background 19F signal from nanoparticles flowing in blood. Magn Reson Med 60:1232–1236, 2008. © 2008 Wiley-Liss, Inc.

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