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Evaluation of Inflammatory Response to Acute Ischemia Using Near-Infrared Fluorescent Reactive Oxygen Sensors

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Abstract

Purpose

Ischemia-related processes associated with the generation of inflammatory molecules such as reactive oxygen species (ROS) are difficult to detect at the acute stage before the physiologic and anatomic evidence of tissue damage is present. Evaluation of the inflammatory and healing response early after an ischemic event in vivo will aid in treatment selection and patient outcomes. We introduce a novel near-infrared hydrocyanine molecular probe for the detection of ROS as a marker of tissue response to ischemia and a precursor to angiogenesis and remodeling. The synthesized molecular probe, initially a non-fluorescent hydrocyanine conjugated to polyethylene glycol, converts to a highly fluorescent cyanine reporter upon oxidation.

Procedures

The probe was applied in a preclinical mouse model for myocardial infarction, where ligation and removal of a portion of the femoral artery in the hindlimb resulted in temporary ischemia followed by angiogenesis and healing.

Results

The observed increase in fluorescence intensity was approximately sixfold over 24 h in the ischemic tissue relative to the uninjured control limb and was attributed to the higher concentration of ROS in the ischemic tissue.

Conclusions

These results demonstrate the potential for non-invasive sensing for interrogating the inflammatory and healing response in ischemic tissue.

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Acknowledgment

The authors appreciate the help of Susannah Grathwohl to implement the HLI method. This research was supported in part by K01RR026095 (WA) from the National Center for Research Resources, National Cancer Institute R21CA149814 (MB), and National Heart Lung and Blood Institute as a Program of Excellence in Nanotechnology (HHSN268201000046C) (MB). SM was supported by the Mallinckrodt Institute of Radiology Summer Research Program. The pulmonology core is supported by NHLBI P50 HL084922 grant from the NIH (RP).

Conflict of Interest

The authors declare no competing financial interest.

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Authors and Affiliations

  1. Department of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Selena Magalotti, Tiffany P. Gustafson, Qian Cao, Mikhail Y. Berezin & Walter J. Akers

  2. Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Dana R. Abendschein & Richard A. Pierce

Authors
  1. Selena Magalotti
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  2. Tiffany P. Gustafson
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  3. Qian Cao
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  4. Dana R. Abendschein
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  5. Richard A. Pierce
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  6. Mikhail Y. Berezin
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  7. Walter J. Akers
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Corresponding authors

Correspondence to Mikhail Y. Berezin or Walter J. Akers.

Additional information

Selena Magalotti and Tiffany P. Gustafson contributed equally to this study.

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Magalotti, S., Gustafson, T.P., Cao, Q. et al. Evaluation of Inflammatory Response to Acute Ischemia Using Near-Infrared Fluorescent Reactive Oxygen Sensors. Mol Imaging Biol 15, 423–430 (2013). https://doi.org/10.1007/s11307-013-0614-2

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  • DOI: https://doi.org/10.1007/s11307-013-0614-2

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