Evaluations of an Early Change in Tumor Pathophysiology in Response to Radiotherapy with Oxygen Enhanced Electron Paramagnetic Resonance Imaging (OE EPRI).

Purpose: Electron Paramagnetic Resonance Imaging (EPRI) can image the partial pressure of oxygen (pO) within in vivo tumor models. We sought to develop Oxygen Enhanced (OE) EPRI that measures tumor pO with breathing gases of 21% O (pO) and 100% O (pO), and the differences in pO between breathing gases (ΔpO). We applied OE EPRI to study the early change in tumor pathophysiology in response to radiotherapy in two tumor models of pancreatic cancer.

Procedures: We developed a protocol that intraperitoneally administered OX071, a trityl radical contrast agent, and then acquired anatomical MR images to localize the tumor. Subsequently, we acquired two pO and two pO maps using the T1 relaxation time of OX071 measured with EPRI and a R-pO calibration of OX071. We studied 4T1 flank tumor model to evaluate the repeatability of OE EPRI. We then applied OE EPRI to study COLO 357 and Su.86.86 flank tumor models treated with 10 Gy radiotherapy.

Results: The repeatability of mean pO for individual tumors was ± 2.6 Torr between successive scans when breathing 21% O or 100% O, representing a precision of 9.6%. Tumor pO and pO decreased after radiotherapy for both models, although the decreases were not significant or only moderately significant, and the effect sizes were modest. For comparison, ΔpO showed a large, highly significant decrease after radiotherapy, and the effect size was large. MANOVA and analyses of the HF10 hypoxia fraction provided similar results.

Conclusions: EPRI can evaluate tumor pO with outstanding precision relative to other imaging modalities. The change in ΔpO before vs. after treatment was the best parameter for measuring the early change in tumor pathophysiology in response to radiotherapy. Our studies have established ΔpO from OE EPRI as a new parameter, and have established that OE EPRI is a valuable new methodology for molecular imaging.