PO₂-based biodosimetry evaluation using an EPR technique acts as a sensitive index for chemotherapy

Area of Science:

• Biomedical Engineering
• Oncology
• Medical Physics

Background:

• Tumor microenvironment oxygen levels critically influence chemotherapy response.
• Understanding dynamic oxygen changes during treatment is vital for optimizing efficacy.
• Breast cancer exhibits altered oxygen partial pressure (PO2) compared to normal tissues.

Purpose of the Study:

• To dynamically monitor tumor microenvironment PO2 using electron paramagnetic resonance (EPR) oximetry before and after chemotherapy.
• To identify the specific time window of peak PO2 following chemotherapy administration.
• To evaluate the impact of PO2-timed chemotherapy on cancer cell apoptosis, tumor volume, and overall treatment efficacy.

Main Methods:

• Implantation of a lithium phthalocyanine probe into MCF-7 human breast cancer cells.
• Transplantation of labeled cells into nude mice models.
• Dynamic PO2 monitoring via EPR oximetry.
• Assessment of mitochondrial enzyme activity (NADH dehydrogenase, succinate-cytochrome c reductase, cytochrome c oxidase).
• Measurement of regional blood flow, cellular apoptosis rates, tumor volume, and tumor inhibitory rates.

Main Results:

• Significantly higher PO2 observed in breast cancer tumors compared to controls.
• Chemotherapy reduced mitochondrial enzyme activity and regional blood flow.
• PO2 peak-based chemotherapy significantly increased apoptosis and tumor volume reduction compared to conventional methods.
• The PO2 peak-based strategy demonstrated a superior tumor inhibitory rate.

Conclusions:

• Timing chemotherapy to an oxygen-rich window maximizes therapeutic response in breast cancer.
• This approach offers a foundation for noninvasive clinical assessment to guide personalized cancer treatment regimens.
• Optimizing treatment based on tumor oxygen dynamics can improve sensitivity monitoring and treatment outcomes.