The emerging field of molecular imaging (MI) aims to noninvasively, quantitatively and repetitively monitor biological processes in vivo to detect disease, probe its basis, and study relevant biochemical pathways at the molecular level. Since molecular targets undergo alterations prior to morphological or physical transformations, MI should aid in early detection and improved diagnosis of disease, resulting in improved clinical outcomes and enhanced long-term patient survival. In addition, the capability to monitor lesion physiology in vivo may facilitate therapeutic efficacy monitoring, speed drug discovery, and potentially lead to patient-specific treatment regimens.
Optical MI, particularly in the near infrared (NIR) wavelength region, is an inexpensive technique that provides relatively high sensitivity without the use of ionizing radiation. Fluorescence imaging is rapid, allowing for dynamic, real-time monitoring of agent biodistribution and clearance profiles and is commonly performed concurrently on multiple animals in a relatively high-throughput manner. The ultimate success of optical MI depends on the development, characterization and optimization of probes as well as superior instrumentation to accurately detect, localize and quantify these unique MI compounds.
The overall objectives of this dissertation were directed at quantitative in vitro and in vivo characterization of two novel MI agents developed in our laboratory: a peripheral benzodiazepine receptor (PBR)-targeted NIR MI agent (NIR-conPK11195) and a potential optical analogue to the 2-[18F]fluoro-2deoxy-D-glucose (18FDG) positron emission tomography agent (NIR-glucosamine). Specific Aims I and II demonstrate the utility of NIR-conPK11195 for breast cancer screening and monitoring as well as for studying breast cancer metastases to the brain, respectively. The dose-dependent and PBR-specific cellular uptake of NIR-conPK11195 can be quantified in live-cell competition assays, visualized by fluorescence microscopy, and monitored in vivo. In Specific Aim III, NIR-glucosamine appears to preferentially label tumor tissue in vivo, but with a potential size and/or vascularity requirement for appreciable tumor-specific contrast. Furthermore, several observations suggest that NIR-glucosamine does not follow the GLUT/hexokinase pathway and may label tumors in a non-specific manner.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-04022007-195749 |
| Date | 13 April 2007 |
| Creators | Wyatt, Shelby Katherine |
| Contributors | Darryl J. Bornhop, Todd D. Giorgio, John C. Gore, E. Duco Jansen, J. Oliver McIntyre |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-04022007-195749/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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