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Related Experiment Video

Updated: Nov 10, 2025

A Bright NIR-II Fluorescence Probe for Vascular and Tumor Imaging
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A NIR fluorescent smart probe for imaging tumor hypoxia.

Kenneth S Hettie1,2, Jessica L Klockow1, Eui Jung Moon3

  • 1Department of Radiology, Stanford University School of Medicine, Stanford, California, USA.

Cancer Reports (Hoboken, N.J.)
|April 3, 2021
PubMed
Summary

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Science advances·2025

A novel hypoxia-sensitive probe, NO2-Rosol, effectively images tumor hypoxia in glioblastoma models. This advancement allows for noninvasive detection of low oxygen levels, crucial for personalized cancer treatment strategies.

Area of Science:

  • Biomedical Imaging
  • Cancer Research
  • Molecular Imaging

Background:

  • Tumor hypoxia, characterized by low oxygen levels, is linked to therapy resistance and poorer patient outcomes.
  • Noninvasive imaging of tumor hypoxia can guide personalized cancer treatments and improve survival rates.
  • A new near-infrared (NIR) fluorescent probe, NO2-Rosol, was developed to detect nitroreductase (NTR) activity as a proxy for hypoxia.

Purpose of the Study:

  • To evaluate the robustness, suitability, and feasibility of the NO2-Rosol probe for imaging hypoxia.
  • To assess NTR activity in diverse glioblastoma (GBM) models under physiologically relevant oxygen levels (pO2 = 2.0%).

Main Methods:

  • Evaluated multiple GBM cell lines for oxygenation sensitivity using carbonic anhydrase IX (CAIX) as a hypoxia surrogate marker.
Keywords:
NIR fluorescencebioimagingglioblastomahypoxiasmart probe

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  • Measured NTR activity with NO2-Rosol in vitro and in vivo tumor hypoxia imaging studies.
  • Assessed probe performance in GBM39 cells and in vivo GBM39 tumor models.

    • Main Results:

    • GBM39 cells exhibited the highest CAIX expression under relevant hypoxic conditions.
    • NO2-Rosol showed an 8-fold fluorescence enhancement in GBM39 cells at pO2 = 2.0%, confirming its suitability.
    • In vivo imaging demonstrated a 5-fold tumor-to-background ratio for NO2-Rosol in GBM39 tumors.

    Conclusions:

    • Established the robustness, suitability, and feasibility of NO2-Rosol for hypoxia imaging.
    • Validated the probe's ability to detect hypoxia in vitro and in vivo under relevant physiological conditions.
    • NO2-Rosol shows promise for noninvasive assessment of tumor hypoxia in glioblastoma models.