Metaboloptics: Visualization of the tumor functional landscape via metabolic and vascular imaging

Area of Science:

• Oncology
• Metabolic Imaging
• Cancer Biology

Background:

• Cancers adapt metabolism to survive fluctuating oxygen levels.
• Existing imaging tools lack the resolution to visualize these metabolic adaptations in vivo.
• Understanding tumor metabolic phenotypes is crucial for developing effective therapies.

Purpose of the Study:

• To develop and validate a high-resolution intravital microscopy technique for imaging cancer metabolism in vivo.
• To quantify glucose uptake, mitochondrial membrane potential (MMP), and oxygen saturation (SO2) in distinct murine breast cancer lines.
• To characterize the in vivo metabolic phenotypes and adaptive behaviors of different breast cancer subtypes.

Main Methods:

• Developed a high-resolution intravital microscopy technique.
• Validated Tetramethyl rhodamine, ethyl ester (TMRE) as a reliable indicator of MMP in vivo.
• Quantified glucose uptake, MMP, and SO2 in three murine breast cancer lines (4T1, 67NR, 4T07) and their microenvironments.
• Assessed metabolic responses to hypoxic stress.

Main Results:

• Metastatic 4T1 tumors exhibited increased glucose uptake (Warburg effect) and elevated MMP across all oxygen levels.
• Non-metastatic 67NR and 4T07 tumors showed increased MMP but comparable glucose uptake to normal tissue.
• 4T1 peritumoral areas displayed a glycolytic shift.
• Under hypoxia, 4T1 tumors increased MMP and decreased SO2, while 4T07 and 67NR tumors shifted to glycolysis.

Conclusions:

• High-resolution intravital microscopy enables detailed characterization of in vivo tumor metabolic phenotypes.
• Distinct metabolic strategies are employed by metastatic versus non-metastatic breast cancer lines.
• Imaging metabolic endpoints within the tumor microenvironment provides critical insights into adaptive tumor behavior and therapeutic vulnerabilities.