Novel Magnetic Resonance Probes

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Novel Magnetic Resonance Probes

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Title: Novel Magnetic Resonance Probes
Author(s):
Hashami, Zohreh
Advisor: Kovacs, Zoltan
Sibert, John W.
Date Created: 2018-05
Format: Dissertation
Keywords: Show Keywords
Abstract: The goal of my first project was the synthesis and characterization of novel DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) based ligands with one and two chromophoric tropone coordinating sidearms for the construction of lanthanide based magnetic resonance/optical imaging probes. Lanthanide ions have nearly identical coordination chemistry properties and therefore, the same ligand can be applied to the entire lanthanide series. The development of dual magnetic resonance/optical imaging probes is an exciting current trend in the research area of lanthanide based imaging agents because these probes could combine the high spatial resolution of MRI with the high sensitivity of optical detection. The challenge in the design of these agents is that the requirements for an efficient MR agent (presence of an inner sphere water molecule) are seemingly incompatible with those of optical agents (absence of inner sphere water molecules). Three ligands were synthesized: 1,4,7,10-tetraazacyclododecane-1,4,7-tris(acetic acid)-10-(2-tropone) (1), 1,4,7,10-tetraazacyclododecane-1,7-bis(acetic acid)-4,10-bis(2-tropone), (2) and 1,4,7,10-tetraazacyclododecane-1,4,7-tris(aceticacid)-10-[2-(4-isopropyl)-tropone) (3) Ln3+complexes of these ligands were found to have one inner-sphere water molecule. The r_1 relaxivity of Gd3+ complexes was found to be similar to that of the commercial Gd-based MRI agents. Relaxivity measurements in the presence of human serum albumin (HSA) showed that the Gd3+ complexes weakly bind to HSA. Variable temperature 17O NMR measurements revealed that the neutral O-donor atom of the tropone moiety slows down the water exchange rate of the Gd3+ complexes compared to that for GdDOTA. In vivo MR imaging experiments with Gd1 and Gd3 in mice revealed that the agents were excreted by the kidneys and the liver. The complexes did not show any toxicity at the injected doses (0.1 mmol/kg). The photophysical properties of the Gd3+, Nd3+ and Yb3+ complexes of ligand 1 and 2 were studied by recording the absorption, excitation and emission spectra. The Nd3+ and Yb3+ complexes were found to exhibit bright NIR emission even in aqueous solutions, which indicates that the tropone unit is an efficient sensitizer for these Ln3+ions. The favorable relaxivity of the Gd3+ complexes and the bright NIR luminescence of the Nd3+ and Yb3+ complexes demonstrate that the tropone chromophore combined with the DOTA framework offers a useful platform for the design of lanthanide-based dual MR/optical imaging agents for in vivo applications. My second project is related to hyperpolarized 13C magnetic resonance spectroscopy/imaging. The goal of this project was the synthesis of monoethyl [4-13C]-oxaloacetate and its evaluation in dissolution dynamic nuclear polarization NMR experiments as a metabolic probe. Monoethyl [4-13C]-oxaloacetate disodium salt was successfully synthesized. Perfused liver experiments revealed that the compound was taken up by the liver, and metabolized to maleate, citrate and aspartate. Dynamic nuclear polarization to enhance the 13C spin polarization was successfully performed, however, the T1 relaxation time of the 13C label at the C4 position was very short (about 14 s), which precluded its in vivo application as a hyperpolarized 13C metabolic probe.
Degree Name: PHD
Degree Level: Doctoral
Persistent Link: http://hdl.handle.net/10735.1/5854
Terms of Use: Copyright ©2018 is held by the author. Digital access to this material is made possible by the Eugene McDermott Library. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Type : text
Degree Program: Chemistry

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