Electron Paramagnetic Resonance Implemented with Multiple Harmonic Detections Successfully Maps Extracellular pH In...

Area of Science:

• Oncology
• Biophysics
• Medical Imaging

Background:

• Extracellular acidification and hypoxia are hallmarks of tumor malignancy.
• Non-invasive extracellular pH (pHe) mapping is crucial for understanding the tumor microenvironment and monitoring drug efficacy.
• Current electron paramagnetic resonance (EPR) methods lack sensitivity for mapping pHe with moderate probe concentrations.

Purpose of the Study:

• To enhance the sensitivity and robustness of EPR-based pHe mapping in preclinical cancer models.
• To investigate the impact of carbonic anhydrase IX (CAIX) inhibition on tumor extracellular pH and growth.

Main Methods:

• Utilized a modified EPR system incorporating multiple harmonic detection (MHD) for improved sensitivity.
• Applied the enhanced EPR technique to mouse xenograft models of human pancreatic ductal adenocarcinoma.
• Administered U-104, a CAIX inhibitor, to assess its effects on tumor growth and pHe.

Main Results:

• The modified EPR system demonstrated a twofold increase in sensitivity for pHe mapping.
• Treatment with the CAIX inhibitor U-104 delayed tumor growth.
• Tumor treatment showed a trend towards increased extracellular acidification.

Conclusions:

• Enhanced EPR with MHD offers a more sensitive and robust method for non-invasive pHe mapping in tumors.
• EPR-based pHe monitoring can effectively track responses to metabolism-targeting drugs like CAIX inhibitors.
• This technology holds promise for developing and evaluating novel metabolism-targeting cancer therapies.