EPR oximetry is likely to benefit significantly from the development of oxygen-sensitive paramagnetic materials with improved characteristics. While the results obtained so far with EPR oximetry indicate that we can meet many of the criteria such as accuracy, sensitivity, and repeatability, there also are a number of potential limitations of the current capabilities. We have found that some of the paramagnetic materials with optimum spectroscopic properties may have some undesirable interactions with tissues, causing reactions and/or losing responsiveness to oxygen. We also have become aware of a need, in some circumstances, to reduce the tendency of small particles to become relocated in tissues through active or passive processes. The overall goal of this research project is to develop and test materials for coating oxygen sensitive paramagnetic materials to enhance their performance as sensors for pO2 in tissues. In order to reach this goal, the following specific aims will be sought: 1) To develop procedures for biocompatible coating paramagnetic oxygen sensors in order to have stable responsiveness of the oxygen sensor as well as to minimize biological reactivity (to develop microencapsulation procedures for different paramagnetic materials and to develop macroscopic films holding the paramagnetic materials in order to have biocompatible oxygen-permeable materials that can be used as retrievable inserts, and as components of implantable resonators and catheters/needle resonators); 2) To test the performance in vivo of these macroscopic sensors in animal models and to assess the effect of long residence in tissues on the performances of the paramagnetic materials and the effect on the biological environment; 3) To further understand the effect of coating on the responsiveness in vivo compared to the uncoated material; to assess the relationship between the nature of the biopolymer, the stability of the responsiveness, and consequently optimize the parameters of the coating preparation; 4) To further study specific packaging considerations (procedures for large batches, influence of sterilization procedures on the performances of the sensors, conditions of storage of the materials).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA091597-07A2
Application #
6661732
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2002-07-29
Project End
2007-06-30
Budget Start
Budget End
Support Year
7
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Demidenko, Eugene (2017) Exact and Approximate Statistical Inference for Nonlinear Regression and the Estimating Equation Approach. Scand Stat Theory Appl 44:636-665
Demidenko, Eugene; Glaholt, S P; Kyker-Snowman, E et al. (2017) Single toxin dose-response models revisited. Toxicol Appl Pharmacol 314:12-23
Hou, Huagang; Li, Hongbin; Dong, Ruhong et al. (2014) Real-time monitoring of ischemic and contralateral brain pO2 during stroke by variable length multisite resonators. Magn Reson Imaging 32:563-9
Borel, Alain; Bean, Jonathan F; Clarkson, Robert B et al. (2008) Towards the rational design of MRI contrast agents: electron spin relaxation is largely unaffected by the coordination geometry of gadolinium(III)-DOTA-type complexes. Chemistry 14:2658-67
Borel, Alain; Kang, Hoon; Gateau, Christelle et al. (2006) Variable temperature and EPR frequency study of two aqueous Gd(III) complexes with unprecedented sharp lines. J Phys Chem A 110:12434-8
Keddie, Daniel J; Johnson, Therese E; Arnold, Dennis P et al. (2005) Synthesis of profluorescent isoindoline nitroxides via palladium-catalysed Heck alkenylation. Org Biomol Chem 3:2593-8
Lan, Minbo; Beghein, Nelson; Charlier, Nicolas et al. (2004) Carbon blacks as EPR sensors for localized measurements of tissue oxygenation. Magn Reson Med 51:1272-8