Direct and Repeated Clinical Measurement of pO 2 for Enhancing Cancer Therapy. 2014 Norris Cotton Cancer Center Comprehensive Thoracic Oncology Program (CTOP) Retreat . Benjamin B. Williams, Ph.D.
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Direct and Repeated Clinical Measurement of pO2 for Enhancing Cancer Therapy
2014 Norris Cotton Cancer Center
Comprehensive Thoracic Oncology Program (CTOP) Retreat
Benjamin B. Williams, Ph.D.
The Geisel School of Medicine at Dartmouth, Departments of Medicine (Radiation Oncology) and Radiology
May 22, 2014
Clinical EPR spectrometer
Subject positioned for oximetry using India ink as reporter
In vivo EPR is sensitive to a wide array of physiologic parameters.
This information is observed through simple changes in the shapes of the detected spectra.
Collisions between the spin probe and molecular O2 promote relaxation and broaden the linewidth of the observed spectrum.
Tatum JL, Kelloff GJ, Gillies RJ, et al. Hypoxia: Importance in tumor Biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy. IntJ Radiat Biol. 2006 Oct;82(10):699-757.
Hockel M, Schelnger K, Aral B, Mitze M, Schaffer U, Vaupel P. Association between Tumor Hypoxia and malignant Progression in Advanced Cancer of the Uterine Cervix. Can Res. 1996 Oct;56:4509-4515.
Eric J. Hall, Amato J. Giaccia. Radiobiology for the radiologist.Lippincott Williams & Wilkins, 2006; 546p.
Timing of dose
Application of pO2modifiers
Points of pO2
Monitor normal tissuesOverall goal
Ink injection and calibrated pO2 response
Tumor pO2 was monitored in melanoma metastases at two sites, in the scalp and neck, during the course of radiation treatment (66 Gy). Spectra were recorded immediately before and after each fraction while the patient inspired room air. These results indicate hypoxic environments that vary on a day-to-day basis, but show little acute response in pO2 due to radiation.pO2 Variability across Serial Measurements
The coupling loop of the implantable resonator is placed subcutaneously and the detection loop(s) are inserted into the tissue of interest.
The implantable resonators can be fabricated with great flexibility in configuration.
Installation for deep tissue measurements of pO2 in the flank of a pig
PROJECT 1:Oxygen measurements in human tumors using EPR oximetry with carbon-based sensors (PI: Gallez)
PROJECT 2: Monitoring of pO2 in human tumors using EPR oximetry with implantable oxygen-sensing probe, OxyChip (PI: Kuppusamy)
PROJECT 3: Oxygen measurements in deep-seated human tumors using EPR oximetry with implantable deep-tissue oxygen sensors (PI: Swartz)
CORE A: Administrative Core
CORE B: Instrument/Resource Core
CORE C: Biostatistics Core
Primary: India ink
Primary: India ink
Oxygen measurements in human tumors using EPR oximetry with carbon-based sensors (PI: Gallez; Sites: Dartmouth, Brussels, Emory, UPenn)
Monitoring of pO2 in human tumors using EPR oximetry with an implantable oxygen-sensing probe (OxyChip) (PI: Kuppusamy; Sites: Dartmouth, Emory)
Oxygen measurements in human tumors using EPR oximetry with implantable deep-tissue oxygen sensors (PI: Swartz; Sites: Dartmouth, Emory)
Harold SwartzLesley Jarvis
Periannan Kuppusamy Phil Schaner
Nadeem Khan Eunice Chen
Huagang Hou Alan Eastman
Ann Flood Eugene Demidenko
Bernard Gallez (UCL, Brussels, Belguim)