Access Type

Open Access Dissertation

Date of Award

1-15-2014

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemistry

First Advisor

Matthew J. Allen

Abstract

The focus of the research described in this thesis is the study of chemistry relevant to target-specific contrast agents for magnetic resonance imaging (MRI). MRI is a widely used technique in diagnostic medicine and biomedical research to obtain anatomical and physiological details of soft tissues. Contrast agents are used to enhance the contrast of MR images by causing changes to the chemical environment of water molecules. Clinically approved GdIII-containing contrast agents for MRI are non-specific, and consequently, have limited utility. Target-specific contrast agents represent one way to circumvent this limitation. In the research described in this thesis, myelin and Β-amyloid aggregates were selected as targets because they are important in diagnosing neurological diseases. The myelin-targeted complexes were designed to mimic the structural features of a known myelin-specific histology stain, and ex vivo mouse-brain staining method was developed to test these complexes. Ex vivo staining studies (optical, MRI, and mass spectrometry imaging) demonstrated the ability of these complexes to interact with the myelinated regions in mouse brain tissue. Additionally, a Β-amyloid-targeted agent was synthesized by conjugating a GdIII-containing complex to curcumin. The binding ability of this complex with in vitro Β-amyloid peptide aggregates was studied using relaxation time and fluorescence measurements. This dissertation presents the synthesis, characterization, and in vitro and ex vivo imaging of these complexes. The studies using these paramagnetic metal complexes have the potential to enable a reliable method to observe structural changes in the brain.

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