| Popis: |
Cancer and neurological disease afflict millions of people in the United States and worldwide. In addition to the heavy toll they take on society, these diseases have devastating bodily consequences. Molecular imaging is a noninvasive means to understand the bodily phenomena driving these diseases and to recognize hopes for treatment. Optical fluorescence imaging is a type of molecular imaging that uses light to probe biological processes and states. Fluorescent contrast agents designed for specific molecular targets report on the status of disease and response to therapy.Myelin is an insulating sheath surrounding axons that aids in nervous signal transduction. Pathologies in myelin are associated with many neurological diseases, most prominently multiple sclerosis. A contrast agent has been evaluated for its ability to bind to myelin in the spinal cord and report on the quantity of myelin sheaths in vitro and in vivo. A novel synthesis of the agent, fluorescent characterization, and application to histological staining is also described. Many chemotherapeutic treatments of cancer damage DNA leading to cell death. To maintain genomic fidelity, cells have evolved multiple pathways to repair DNA damage. These pathways are active in cancer cells and can limit the therapeutic efficacy of DNA damaging drugs. One notable repair pathway is base excision repair, which excises chemically damaged bases. Optical imaging probes have been designed, synthesized, and characterized for their ability to bind to the first intermediate of the base excision repair pathway, the abasic (or AP) site. An assay has been developed to evaluate AP site-targeted probes. Their ability to report on physiologically relevant quantities of AP sites has been established in tissue culture. While this work focuses on AP sites in cancer, base excision repair is also relevant to neurological diseases including Alzheimer’s and Parkinson’s diseases.The optical imaging probes targeted to myelin and AP sites have potential preclinical application in new drug discovery. They can also be further developed to monitor response to therapy either in cell culture or animal models of disease. The probes could also be modified for combination use with additional imaging modalities for application in a clinical setting. |
