Noninvasive imaging of infection after treatment with tumor-homing bacteria using Chemical Exchange Saturation Transfer (CEST) MRI

Authors

  • Guanshu Liu,

    Corresponding author
    1. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA
    2. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    • Correspondence to: Guanshu Liu, Ph.D., Kennedy Krieger Institute, F.M. Kirby Research Center, 707 N. Broadway, Baltimore, MD 21205. E-mail: guanshu@mri.jhu.edu

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  • Chetan Bettegowda,

    1. Ludwig Center, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Baltimore, Maryland, USA
    2. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Yuan Qiao,

    1. Ludwig Center, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Baltimore, Maryland, USA
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  • Verena Staedtke,

    1. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Kannie W.Y. Chan,

    1. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Renyuan Bai,

    1. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Yuguo Li,

    1. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Gregory J. Riggins,

    1. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Kenneth W. Kinzler,

    1. Ludwig Center, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Baltimore, Maryland, USA
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  • Jeff W.M. Bulte,

    1. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA
    2. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    3. Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Michael T. McMahon,

    1. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA
    2. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Assaf A. Gilad,

    1. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Bert Vogelstein,

    1. Ludwig Center, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Baltimore, Maryland, USA
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  • Shibin Zhou,

    1. Ludwig Center, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Baltimore, Maryland, USA
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  • Peter C.M. van Zijl

    1. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA
    2. Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Abstract

Purpose

To develop a noninvasive MRI method for determining the germination and infection of tumor-homing bacteria in bacteriolytic cancer therapy using endogenous CEST contrast.

Methods

The CEST parameters of the anaerobic gram-positive bacterium Clostridium novyi-NT (C. novyi-NT) were first characterized in vitro, then used to detect C. novyi-NT germination and infection in subcutaneous CT26 colorectal tumor-bearing mice (n = 6) after injection of 300 million bacterial spores. Lipopolysacharide (LPS) injected mice were used to exclude that the changes of CEST MRI were due to inflammation.

Results

CEST contrast was observed over a broad frequency range for bacterial suspensions in vitro, with the maximum contrast around 2.6 ppm from the water resonance. No signal could be detected for bacterial spores, demonstrating the specificity for germination. In vivo, a significant elevation of CEST contrast was identified in C. novyi-NT infected tumors as compared to those before bacterial germination and infection (P < 0.05; n = 6). No significant change was observed in tumors with LPS-induced sterile inflammation (P > 0.05; n = 4).

Conclusion

Endogenous bacterial CEST contrast (bacCEST) can be used to monitor the germination and proliferation of the therapeutic bacterium C. novyi-NT without a need for exogenous cell labeling probes. Magn Reson Med 70:1690–1698, 2013. © 2013 Wiley Periodicals, Inc.

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