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Quantitative In Vitro and In Vivo Characterization of Near Infrared Molecular Imaging Agents for Enhanced Disease Detection

dc.creatorWyatt, Shelby Katherine
dc.date.accessioned2020-08-22T00:22:01Z
dc.date.available2008-04-13
dc.date.issued2007-04-13
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-04022007-195749
dc.identifier.urihttp://hdl.handle.net/1803/11924
dc.description.abstractThe 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.
dc.format.mimetypeapplication/pdf
dc.subjectperipheral benzodiazepine receptor
dc.subjectcancer
dc.subjectnear infrared
dc.subjectoptical
dc.subjectmolecular imaging
dc.subjectPBR
dc.subjectNear infrared spectroscopy
dc.subjectBreast -- Cancer -- Imaging
dc.subjectFluorescence microscopy
dc.subjectBrain -- Cancer -- Imaging
dc.subjectBenzodiazepines -- Receptors -- Diagnostic use
dc.subjectMolecular probes
dc.titleQuantitative In Vitro and In Vivo Characterization of Near Infrared Molecular Imaging Agents for Enhanced Disease Detection
dc.typedissertation
dc.contributor.committeeMemberJohn C. Gore
dc.contributor.committeeMemberE. Duco Jansen
dc.contributor.committeeMemberJ. Oliver McIntyre
dc.type.materialtext
thesis.degree.namePHD
thesis.degree.leveldissertation
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorVanderbilt University
local.embargo.terms2008-04-13
local.embargo.lift2008-04-13
dc.contributor.committeeChairDarryl J. Bornhop
dc.contributor.committeeChairTodd D. Giorgio


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