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Nanoparticles as signaling agents for magnetic resonance imaging and scintillation counting

Posted on:2008-09-30Degree:Ph.DType:Dissertation
University:University of KentuckyCandidate:Zhu, DonghuaFull Text:PDF
GTID:1444390005477171Subject:Chemistry
Abstract/Summary:
The focus of the author's dissertation was on developing nanoparticles that serve as basic vectors of novel signaling agents. These include applications in magnetic resonance imaging (Part I) where gadolinium (Gd) bound nanoparticles were used as a macromolecular contrast agent for the enhancement of cancer imaging and detection, and in scintillation counting (Part II) where fluor-containing nanoparticle suspensions were used to quantify various alpha and beta - emitting radionuclides by aqueous liquid scintillation counting.; Nanoparticles with Gd bound to their surface composed of various formulation materials such as Emulsifying Wax NF, Brij 78, a phospholipid-chelate (PE-DTPA) and a pegylated phospholipid (DSPE-PEG) were engineered from oil-in-water microemulsion templates using the Nanotemplate Engineering(TM) approach. In addition to small particle size and uniform Gd surface distribution, these nanoparticles were shown to have appropriate stability, enhanced relaxivities, sufficient binding affinity and kinetic inertness under physiological conditions. Following administration of these nanoparticles to tumor-bearing mice, contrast enhancement of T1 weighted images was observed and the accumulation of Gd in tumor regions was consistent with the estimated value obtained by T1 measurement using MR imaging. The Gd plasma concentration of Gd-nanoparticles over a period of 24 hours followed a two compartmental model with Clsys = 0.89 mL/hour and MRT = 6 hour. These readily manufacturable nanoparticles were shown to offer great potential as a next-generation MRI contrast agent.; Based on our experience of using nanoparticles to enhance the apparent water solubility of hydrophobic drugs, we prepared fluor-containing nanoparticles from oil-in-water microemulsions in which styrene/divinylbenzene comprised the oil phase. The resulting nanoparticle suspension qualified as non-hazardous waste by testing against U.S. Environmental Protection Agency standards for reactivity, pH, ignitability and Toxicity Characteristic Leaching. The nanoparticles suspension was then used to quantify 14C in various sample matrices by aqueous liquid scintillation counting. It exhibited greater quench resistance than a conventional organic cocktail and was very efficient at detecting higher energy alpha and beta- emitting radionuclides. A polymerizable scintillant was prepared to prevent leaching of fluor molecules. The relationship between particle size, kinetic energy of beta- particles and counting efficiency was simulated by a theoretical model. These results indicate this aqueous fluor-containing nanoparticle suspension can be used in place of conventional organic solvent-based liquid scintillation cocktails and eliminate the costs and negative environmental consequences of mixed waste disposal.; Keywords: Nanoparticles, Magnetic Resonance Imaging, Liquid Scintillation Counting, Gadolinium, Oil-in-water microemulsion.
Keywords/Search Tags:Nanoparticles, Magnetic resonance imaging, Scintillation counting
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