Evaluation of Inflammatory Response to Acute Ischemia Using Near-Infrared Fluorescent Reactive Oxygen Sensors
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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.
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.
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.
These results demonstrate the potential for non-invasive sensing for interrogating the inflammatory and healing response in ischemic tissue.
Key wordsCardiovascular disease Optical imaging Activatable Hindlimb ischemia Molecular imaging
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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