POLYMERIC ELECTRON PARAMAGNETIC RESONANCE PROBES FOR REAL-TIME MONITORING OF TISSUE VASCULARIZATION

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Program Director/Principal Investigator (Last, First, Middle): GUAN, JIANJUN Project Summary The objective of this proposal is to create bioeliminable and injectable hydrogel-based electron paramagnetic resonance (EPR) probes that can be implanted for the real-time and long-term measurement of tissue oxygen (O2) concentration. The purpose is to monitor the ischemic tissue vascularization process during therapy. Ischemic diseases, resulting from reduced blood supply, lead to serious damage and injury of various tissues and organs. The primary therapeutic goal for ischemic diseases is to vascularize the ischemic tissues to restore blood flow. To quickly, conveniently, and accurately evaluate the efficacy of the therapy, real-time and reproducible monitoring of tissue O2 concentration changes at the same tissue location by a minimally invasive or non-invasive spectroscopic approach represents a compelling strategy. However, this cannot be achieved by any clinically available approaches. Current approaches are either unable to provide real-time and long-term measurements under ischemic conditions or invasive. Among the different techniques for tissue O2 concentration measurement, EPR has the potential to achieve this goal. EPR has distinct advantages over other techniques, such as the ability to measure tissue O2 concentration without consuming O2, and to provide absolute values even at low O2 concentration environment. However, until now there is a lack of suitable EPR probes that can maintain a consistent concentration in tissues for an extended period (≥ 4 weeks), and can be implanted and/or retrieved by a minimally invasive approach. The proposed work addresses the critical need for bioeliminable, non-toxic, and long-lasting EPR probes that can be implanted by a minimally invasive approach for the long-term monitoring of tissue O2 concentration. This is highly novel and similar EPR probes have not been developed previously. The proposed hydrogel-based EPR probes will not only be injectable and bioeliminable, but also feature a fast gelation rate, a slow weight loss rate, high O2 permeability, and high EPR sensitivity. The injectable hydrogels can be implanted into tissues by a minimally invasive injection approach. The hydrogel-based EPR probes will have high molecular weight, and this will overcome the toxicity issue of commonly used small molecule EPR probes. Furthermore, they can be removed from the body after becoming water soluble by hydrolysis of side groups, thereby eliminating the need for retrieval. The hydrogels will be designed to have high gelation rate to achieve high retention in tissues. The probes with slow weight loss rate will maintain the EPR signal intensity for an extended period of time while retaining in a certain tissue location, allowing for long-term monitoring of O2 concentration. The high O2 permeability and EPR sensitivity will ensure that a small change in O2 concentration can be monitored in real-time. AIM #1 will create bioeliminable and injectable hydrogel-based EPR probes with a fast gelation rate, a slow weight loss rate, high oxygen permeability, and high EPR sensitivity. AIM #2 will test the hypothesis that the developed hydrogel-based EPR probe will allow continuous monitoring of tissue oxygen concentration using an ischemic limb model. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page