Multimodal Marker for imaging oximetry in radiotherapy

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PROJECT SUMMARY Despite the clinical significance and importance of tissue oxygen levels in the diagnosis, prognosis, and treatment of several pathologies, currently there is clearly an unmet need for methods to quantify tissue oxygen levels with a reasonable degree of accuracy, reliability, and robustness required for use in the clinical settings. The overall objective of this proposal is to bring the unique capability of electron paramagnetic resonance (EPR) oximetry to the clinical realm, particularly for enhancement of cancer treatment. We have discovered unique solid-state sensors, called OxyChips and procedures that enable unsurpassed reliability and repeated interrogation of tissue oxygen levels at specific tissue sites over a period—possibly indefinitely. However, these sensors are limited primarily to laboratory research involving small animals. We have observed—in a small cohort of cancer patients—that translation of this novel technology to clinical applications would require innovative sensors to provide enhanced detection capability, safety, stability, and robustness as a routine clinical tool. We propose to develop a novel class of the OxyChip sensor with enhanced detection sensitivity, easy identification during clinical imaging, and long-term safety and stability—all specifically designed and optimized for measurement in deeper tumors. The proposed developments, combined with the unique capabilities of the EPR oximetry technology, will be a valuable clinical tool capable of providing real- time knowledge of tumor oxygen levels for enhanced cancer treatments and clinical outcomes. The following specific aims are proposed: (1) Characterization of OxyChips to establish their suitability for temporal and spatial localization in routine clinical imaging. The OxyChips embedded with GNP will be subjected to careful evaluation under clinically relevant imaging conditions to determine its suitability for temporal and spatial localization during routine clinical imaging. Evaluation will include regional conspicuity (i.e., visibility of OxyChip with respect to its local tumor environment), quantitative measure of detectability, (i.e., signal-to-noise ratio and contrast-to-noise ratio), and image processing methods for visual and quantitative enhancement of the OxyChips. (2) Evaluation of the new OxyChips embedded with GNP in a pre-clinical rabbit tumor model to establish their safety, robustness, and utility for imaging and oxygen measurements in the clinical settings. We will determine the capability of the new sensors for clinical applicability using rabbit breast tumor model. The evaluation criteria will include visualization of the sensors in the tumor using clinical imaging modalities, such as CT, CB-CT, planar X-ray, and ultrasound. The proposed research will further advance the capability of EPR oximetry with OxyChip for cancer treatment.