How best to interpret measures of levels of oxygen in tissues to make them effective clinical tools for care of patients with cancer and other oxygen‐dependent pathologies

Abstract

It is well understood that the level of molecular oxygen (O 2 ) in tissue is a very important factor impacting both physiology and pathological processes as well as responsiveness to some treatments. Data on O 2 in tissue could be effectively utilized to enhance precision medicine. However, the nature of the data that can be obtained using existing clinically applicable techniques is often misunderstood, and this can confound the effective use of the information. Attempts to make clinical measurements of O 2 in tissues will inevitably provide data that are aggregated over time and space and therefore will not fully represent the inherent heterogeneity of O 2 in tissues. Additionally, the nature of existing techniques to measure O 2 may result in uneven sampling of the volume of interest and therefore may not provide accurate information on the “average” O 2 in the measured volume. By recognizing the potential limitations of the O 2 measurements, one can focus on the important and useful information that can be obtained from these techniques. The most valuable clinical characterizations of oxygen are likely to be derived from a series of measurements that provide data about factors that can change levels of O 2 , which then can be exploited both diagnostically and therapeutically. The clinical utility of such data ultimately needs to be verified by careful studies of outcomes related to the measured changes in levels of O 2 .

Oxygenation Status of Malignant Tumors vs. Normal Tissues: Critical Evaluation and Updated Data Source Based on Direct Measurements with pO2 Microsensors

“…Nevertheless, they give a rough picture of the situation with which the clinician is confronted during tumor detection and therapy. Assessment of the size of hypoxic sub-volumes and different severity of hypoxia in tumors, therefore, should be a "sine qua non" condition before and during treatment to guarantee effective personalized (individualized) therapy [8].…”

OxyChip Implantation and Subsequent Electron Paramagnetic Resonance Oximetry in Human Tumors Is Safe and Feasible: First Experience in 24 Patients

“…Other considerations impact the decision to use differently sized OxyChips, most prominently the issue of hypoxia heterogeneity within a given tumor. Heterogeneity of oxygenation within tumors is a complex issue, as it can vary spatially and temporally and is influenced by underlying pathology as well as anti-neoplastic therapies (17). The OxyChip has unique advantages in terms of assessing temporal changes in hypoxia via EPR oximetry, as the pO 2 can be repeated measured non-invasively as often as desired, but the measurement is limited to the small volume of tissue surrounding the OxyChip.…”

NIH Workshop 2018: Towards Minimally Invasive or Noninvasive Approaches to Assess Tissue Oxygenation Pre- and Post-transfusion

“…Electron paramagnetic resonance (EPR) oximetry can make direct and repeated measurements of tissue oxygen in both preclinical models and human subjects [33]. This involves a one-time, minimally invasive, injection of appropriate paramagnetic materials into the target of interest.…”