Caltech Library System

About | Browse | Search | Caltech Student Instructions

Type of Document	Dissertation
Author	Allen, Matthew John
URN	etd-12122003-094113
Persistent URL	http://resolver.caltech.edu/CaltechETD:etd-12122003-094113
Title	Delivery and activation of contrast agents for magnetic resonance imaging
Degree	PhD
Option	Chemistry
Advisory Committee	Advisor Name Title John Bercaw Committee Chair Harry Gray Committee Member Scott Fraser Committee Member Thomas Meade Committee Member
Keywords	gadolinium Alzheimer's disease polyarginine
Date of Defense	2003-12-09
Availability	unrestricted
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.
Files	Filename       Size       Approximate Download Time (Hours:Minutes:Seconds)     28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access    TotalThesis.pdf 1.45 Mb 00:06:44 00:03:27 00:03:01 00:01:30 00:00:07