Delivery and Activation of Contrast Agents for Magnetic Resonance Imaging

Citation

Allen, Matthew John (2004) Delivery and Activation of Contrast Agents for Magnetic Resonance Imaging. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/6V70-FK81. https://resolver.caltech.edu/CaltechETD:etd-12122003-094113

Abstract

Magnetic Resonance Imaging (MRI) has become a powerful tool for noninvasive imaging of living specimens. Magnetic resonance contrast agents containing the paramagnetic ion gadolinium(III) are used to enhance regions, tissues, and cells that are magnetically similar but histologically distinct. To increase the effectiveness of contrast agents, agents responsive to biological phenomena and directed to specific regions need to be developed. These two improvements are related in that many biologically significant molecules are located in specific locations. Therefore, the design, synthesis, and testing of advanced contrast agents are described.

Many interesting biological targets for imaging reside inside the cell membrane. As the current generation of contrast agents is strictly extracellular, a method of intracellular delivery is required in the development of MRI contrast agents. I have developed cationic, polyarginine-oligomers to deliver gadolinium(III)-based contrast agents into the interior of cells. Delivery was confirmed and studied using methods including inductively coupled plasma-mass spectrometry, MRI, and two-photon laser microscopy to image lanthanide-based MRI contrast agents.

A second approach focused on the synthesis of a series of contrast agents designed to cross the blood brain barrier and label A[Beta]-plaques associated with Alzheimer's disease. These agents were found to permeate cell membranes, and the intracellular properties of these agents are compared to the polyarginine agents. Finally, attempts towards the creation of an advanced MRI contrast agent that is chemically activated by matrix metalloproteinases are described.

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