Doctoral Dissertations

Date of Award

5-1990

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Chemistry

Major Professor

George W. Kabalka

Committee Members

D. C. Kleinfelter, Charles Feigerle, Leaf Huang

Abstract

Gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) has been extensively investigated as a contrast enhancement agent for MRI because of its low toxicity and high spin number (7/2). The high solubility and rapid excretion of Gd- DTPA make it an ideal agent for mapping vascular spaces and leakage through the blood-brain barrier. However, it is limited in value for imaging the liver since the complex does not accumulate in that organ. Recently, in order to extend its utility toward contrast enhancement of the liver, a Gd-DTPA derivative which contained hydrophobic alkyl chains that were connected to the ionic polar moiety via an amide linkage was developed and used to construct a new class of paramagnetic gadolinium-labeled liposomes (GLL). This agent effectively enhanced the T1 relaxation of liver tissue. However, it exhibited a very long retention time in that organ. In this work, new Gd-DTPA derivatives were developed to be utilized as GLL agents that would retain the relaxation properties of the previous Gd-DTPA amide derivative but also exhibit a shorter biological lifetime. This was accomplished utilizing two approaches: the existing Gd-DTPA amide complex was modified by decreasing the length of the hydrophobic alkyl chains and new Gd-DTPA derivatives were developed that would degrade more rapidly into Gd-DTPA residues. The preparation, biological clearance rate and contrast enhancing abilities of these new agents are discussed. Boron neutron capture therapy (BNCT) is brachyradiotherapy by heavy charged particles which depends on the successful delivery of agents enriched with the boron-10 isotope to a targeted organ or lesion. A current problem associated with BNCT is the inability to noninvasively verify, localize and quantitate in-vivo boron content. Magnetic resonance spectroscopy (MRS) and imaging (MRI) are potentially valuable techniques for the non-invasive evaluation of BNCT agents in-vivo. In this work, boron-11 magnetic resonance techniques were developed for the detection and localization of a representative BNCT agent in solution as well as in animal tissue. The results of these endeavors, from both a spectroscopic and imaging standpoint, as well as the problems encountered when attempting to achieve these purposes are discussed.

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