Imaging tumor extracellular pH using PET/MRI co-agents

Motivation: Tumor acidosis is a key biomarker for diagnosing cancer and monitoring treatment response. Non-invasive techniques for measuring tumor extracellular pH (pHe) are limited and not yet clinically routine. Goal(s): This study aimed to evaluate a novel approach using simultaneous PET/MRI with 18F and 68Ga based co-agents to accurately measure tumor pHe. Approach: We synthesized pH-sensitive 68Ga and 18F PET/MRI co-agents and measured tumor pHe in a metastatic breast cancer mouse model with pre- and post-bicarbonate treatment. Results: Both agents successfully measured pHe with promising accuracy. The 18F co-agents demonstrated higher precision, with results closely matching those from gold-standard pH sensors. Impact: This dual PET/MRI approach provides a reliable, non-invasive method for measuring tumor pHe, potentially transforming how tumor acidosis is monitored. It could lead to earlier, more accurate assessments of treatment response, enhancing personalized cancer therapy strategies.