Hypoxia imaging in cells and tumor tissues using a highly selective fluorescent nitroreductase probe

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Cancer Diagnostics

Background:

• Hypoxia is prevalent in advanced solid tumors due to oxygen supply-demand imbalance.
• Increased nitroreductase (NTR) expression is observed in hypoxic tumors.
• Targeting NTR is crucial for developing selective hypoxia detection probes.

Purpose of the Study:

• To design and evaluate a novel fluorescent probe for selective NTR detection.
• To assess the probe's efficacy for in vitro and in vivo hypoxia imaging.
• To demonstrate the probe's potential in cancer diagnostics.

Main Methods:

• Synthesis and characterization of a novel fluorescent probe (1).
• In vitro evaluation of probe response to NTR using rat liver microsomes.
• In vivo imaging in Caenorhabditis elegans (C. elegans) models.
• Hypoxia detection in HI5 cells and a murine tumor model.

Main Results:

• Probe (1) exhibited NTR-catalyzed reduction, leading to fluorescence enhancement.
• Selective fluorescence increase was observed due to NTR-mediated bond cleavage.
• Successful in vitro and in vivo detection of NTR and hypoxia was achieved.
• Probe (1) demonstrated efficacy in cell and animal models.

Conclusions:

• The developed fluorescent probe enables selective optical detection of NTR.
• Probe (1) is effective for in vivo imaging and diagnosing tumor hypoxia.
• This probe holds significant potential for fluorescence bioimaging and clinical applications.