8 research outputs found
First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip
Objective: The overall objective of this clinical study was to validate an implantable oxygen sensor, called the ‘OxyChip’, as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing. Methods: Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO2) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry. Results: Twenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4–128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO2 values were variable with overall median 15.7 mmHg (range 0.6–73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO2 was 31.8 mmHg (range 1.5–144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation. Conclusions: Measurement of baseline pO2 and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes
Variable radio frequency proton–electron double-resonance imaging: Application to pH mapping of aqueous samples
Organ specific mapping of in vivo redox state in control and cigarette smoke-exposed mice using EPR/NMR co-imaging
Variable Field Proton–Electron Double-Resonance Imaging: Application to pH mapping of aqueous samples
<i>In Vivo</i> Proton–Electron Double-Resonance Imaging of Extracellular Tumor pH Using an Advanced Nitroxide Probe
A variable radio frequency proton–electron
double-resonance
imaging (VRF PEDRI) approach for pH mapping of aqueous samples has
been recently developed (Efimova
et al. J. Magn. Reson. 2011, 209, 227−232). A pH map is extracted from two PEDRI acquisitions performed at
electron paramagnetic resonance (EPR) frequencies of protonated and
unprotonated forms of a pH-sensitive probe. To translate VRF PEDRI
to an <i>in vivo</i> setting, an advanced pH probe was synthesized.
Probe deuteration resulted in a narrow spectral line of 1.2 G compared
to a nondeuterated analogue line width of 2.1 G allowing for an increase
of Overhauser enhancements and reduction in rf power deposition. Binding
of the probe to the cell-impermeable tripeptide, glutathione (GSH),
allows for targeting to extracellular tissue space for monitoring
extracellular tumor acidosis, a prognostic factor in tumor pathophysiology.
The probe demonstrated pH sensitivity in the 5.8–7.8 range,
optimum for measurement of acidic extracellular tumor pH (pH<sub>e</sub>). <i>In vivo</i> VRF PEDRI was performed on Met-1 tumor-bearing
mice. Compared to normal mammary glands with a neutral mean pH<sub>e</sub> (7.1 ± 0.1), we observed broader pH distribution with
acidic mean pH<sub>e</sub> (6.8 ± 0.1) in tumor tissue. In summary,
VRF PEDRI in combination with a newly developed pH probe provides
an analytical approach for spatially resolved noninvasive pH<sub>e</sub> monitoring, <i>in vivo</i>