Letting Biology Validate the EPR Imaging of Tumor pO₂

Hypoxic resistance of living tissue to cytotoxin, most notably radiation, has been known for over a century but was believed in early trials to be a universal characteristic of all tumors. Oxygen electrode measurements of tumor pO₂ demonstrated that many tumors had insufficient hypoxia to affect tumor resistance. Electron paramagnetic resonance oxygen images have been shown to accurately quantify and locate tumor hypoxia. Using novel radiation delivery for preclinical models with isocentric tumor boosts using 3D printed radiation apertures, we compared tumor control after equivalent integral dose boosts-either to hypoxic tumor or to well-oxygenated tumor-in preclinical models. For the first time, in three preclinical tumor models, we demonstrated a significant advantage for hypoxic boosts relative to well-oxygenated boosts.