Author: Jorge De La Cerda, Andrew Joseph Fanning, Tianzhe Li, Xiaofei Liang, Grace Murley, Mark Pagel, William Schuler, Renee Tran, Shuo Wang, Su-Min Zhou 👨🔬
Affiliation: University of Wisconsin Madison, University of Nebraska Medical Center, University of Texas MD Anderson Cancer Center 🌍
Purpose: Electron paramagnetic resonance imaging (EPRI) can be used to image partial pressure of oxygen (pO2) in tumor models. The goal of this study is to develop an Oxygen Enhanced EPRI protocol to measure tumor pO2 with breathing gas of medical air (21% O2) and pure oxygen (100% O2), and the difference in pO2 between breathing gases (ΔpO2). We utilized the methodology to study the early change in tumor physiology in response to radiation in two in vivo tumor models of pancreatic cancer.
Methods: We developed a protocol that intraperitoneally administered a trityl radical contrast agent (OX071), and then acquired anatomical MR images for tumor localization and image registration. We acquired two pO221% and two pO2100% maps using the T1 relaxation time of OX071 measured with EPRI and a R1-pO2 calibration of OX071. We evaluated the difference between these maps (ΔpO2). We studied 4T1 flank tumor model to evaluate the repeatability of OE EPRI. We then applied OE EPRI to study mice implanted with COLO 357 and Su.86.86 pancreatic ductal adenocarcinoma that were treated with 10 Gy radiotherapy.
Results: pO2 results showed the repeatability of ±2.6 Torr for pO2 measurement in individual tumors, which corresponds to a precision of 9.6%. Tumor pO221% and pO2100% both decreased after radiation for both models, although the decreases were only moderately significant, and the effect sizes were modest. Nevertheless, ΔpO2 showed a large, highly significant decrease after radiation.
Conclusion: EPRI can evaluate tumor pO2 with outstanding precision. The change in ΔpO2 before vs. after treatment was the best marker for measuring the early change in tumor pathophysiology in response to radiation in mice. Our studies have established OE EPRI as a valuable new methodology for molecular imaging.