Biologically-compatible gadolinium(at)(carbon nanostructures) as advanced contrast agents for magnetic resonance imaging

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dc.contributor.advisorWilson, Lon J.en_US
dc.creatorSitharaman, Balajien_US
dc.date.accessioned2009-06-04T08:36:24Zen_US
dc.date.available2009-06-04T08:36:24Zen_US
dc.date.issued2005en_US
dc.description.abstractParamagnetic gadolinium-based carbon nanostructures are introduced as a new paradigm in high-performance magnetic resonance imaging (MRI) contrast agent (CA) design. Two Gd C60-based nanomaterials, Gd C60 [C(COOH)2]10 and Gd C60(OH)x are shown to have MRI efficacies (relaxivities) 5 to 20 times larger than any current Gd3+-based CA in clinical use. The first detailed and systematic physicochemical characterization was performed on these materials using the same experimental techniques usually applied to traditional Gd 3+-based CAs. Water-proton relaxivities were measured for the first time on these materials, as a function of magnetic field (5 x 10-4--9.4 T) to elucidate the different interaction mechanisms and dynamic processes influencing the relaxation behavior. These studies attribute the observed enhanced relaxivities completely to the "outer sphere" proton relaxation mechanism. These "outer sphere" relaxation effects are the largest reported for any Gd3+-based agent without inner-sphere water molecules. The proton relaxivities displayed a remarkable pH-dependency, increasing dramatically with decreasing pH (pH: 3--12). The increase in relaxivity resulted mainly from aggregation and subsequent three-order-of-magnitude increase in tauR, the rotational correlation time. Water-soluble fullerene materials (such as the neuroprotective fullerene drug, C3) readily cross cell membranes, suggesting an application for these gadofullerenes as the first intracellular, as well as pH-responsive MRI CAs. Studies performed at 60 MHz in the presence of phosphate-buffered saline (PBS, mice serum pH: 7.4) to mimic physiological conditions demonstrated that the aggregates can be disrupted by addition of salts, leading to a decrease in relaxivity. Biological fluids present a high salt concentration and should strongly modify the behavior of any fullerenes/metallofullerene-based drug in vivo. Gd C60[C(COOH)2]10 also showed enhanced relaxivity (23% increase) in the presence of the blood protein, human serum albumin (HSA). This result suggests a strong non-covalent interaction between Gd C60[C(COOH)2]10 and HSA leading to slower rotation and a subsequent increase in relaxivity. This also suggests Gd C 60[C(COOH)2]10 as a promising candidate for non-invasive MR angiographic applications to image the "blood pool." Finally, the various important factors or parameters discussed in this work provide valuable insight that can, in general, be used not only for the development of other carbon nanostructure-based MRI contrast agents, but also for any fullerene-based biomedical application.en_US
dc.format.extent92 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS CHEM. 2005 SITHARAMANen_US
dc.identifier.citationSitharaman, Balaji. "Biologically-compatible gadolinium(at)(carbon nanostructures) as advanced contrast agents for magnetic resonance imaging." (2005) Diss., Rice University. <a href="https://hdl.handle.net/1911/18817">https://hdl.handle.net/1911/18817</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/18817en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectEngineeringen_US
dc.subjectMaterials scienceen_US
dc.titleBiologically-compatible gadolinium(at)(carbon nanostructures) as advanced contrast agents for magnetic resonance imagingen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemistryen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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