Synthesis of Bio-Inorganic Tracers for Diagnostic Radiol

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Molecular and cellular imaging is a rapidly developing field whose results have the potential to contribute to the successes of cellular therapies. The development and testing of novel tools, reagents, and methods to image specific molecular pathways in vivo, particularly those that are key targets in disease processes may further the understanding of the pathology. The intrinsic magnetic resonance image (MRI) contrast of tissues can be augmented by the use of contrast agents (CA) in both clinical and experimental settings. CA increases the 1/T-1 and 1/T-2, often referred to as the inner and outer sphere relaxation water in the case of in vivo MRI. Inner sphere relaxation is enhanced by increasing the primary water-metal interaction, while outer sphere relaxation is enhanced by increasing the primary water-secondary water interaction. The current 1/T-1 FDA approved contrast agents are all Gadolinium (Gd) based. Their contrast enhancement in the primary cardiovascular system is merely satisfactory and severely limited by the short retention time of these compounds in the subject. Thus, the development of Gd-based 1/T-1 contrast agents, with greater contrast enhancement or increased retention times, is the basis for this research collaboration. Current research has yielded the synthesis of a novel Gd-, Calix-arene compound which can potentially interact with human serum albumin through electrostatic interactions, leading to increased retention times in the cardiovascular system for more in depth imaging by MRI. Thorough characterization of this new synthetic product, and all synthetic steps leading to it, has been accomplished. Future work includes insertion of Gd, stability testing and relaxation measurements to determine the compounds potential as an imaging agent. While progress continues on the development of the calix-arene compound and the successful insertion of gadolinium, further characterization of iron oxide T2 imaging agents, currently used in cell labeling, was completed. Superparamagnetic Iron Oxide (SPIO) nanoparticles, either modified or in combination with other macromolecules, are being used for magnetic labeling of stem cells and other cells to monitor cell trafficking by Magnetic Resonance Imaging (MRI) in experimental models. The correlation of histology to MRI depends on the ability to detect SPIO labeled cells using Prussian blue (PB) stain and fluorescent tags to cell surface markers. Exposure of PB positive sections to ultraviolet light at a wavelength of 365 nanometers commonly used in fluorescence microscopy can result in color transformation of PB positive material from blue to brown. Although this color transformation is primarily an artifact that may occur during fluorescence microscopy, when the color transformation occurs of PB weakly positive cells and when this is used in combination with image processing, the detection of low levels of iron labeled cells in tissues samples can be correlated to cellular MRI.