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|Title:||The design, syntheses, and physico-chemical studies of MRI contrast agents|
|Author(s):||Marumoto, Alan Kazunari|
|Doctoral Committee Chair(s):||Lauterbur, Paul C.|
|Department / Program:||Chemistry|
|Degree Granting Institution:||University of Illinois at Urbana-Champaign|
|Abstract:||Magnetic Resonance Imaging (MRI) is a popular and powerful clinical diagnostic tool. The development of MRI contrast agents allows for even greater diagnostic ability. This thesis will address the design, syntheses and physico-chemical studies of two specific classes of MRI contrast agents: the DTPA bisamide macrocycles and the bile salt-like hepatobiliary targeted contrast agents.
The DTPA bisamide macrocycles are synthesized from the condensation product of DTPA biscyclic-dianhydride with an appropriate 1,N-diaminoalkane. Physical properties such as metal binding and albumin binding as well as imaging studies, demonstrated that small DTPA bisamide macrocycles (15-18 member macrocycles) do not bind Gd(3+) as strongly as the linear DTPA derivatives. In addition, imaging studies demonstrated breast tumor and kidney enhancement.
Nuclear Magnetic Resonance Dispersions (NMRD) were measured in hypotonic, isotonic, and hypertonic solutions with and without albumin present. The results of the NMRD coupled with the albumin binding studies indicate that the albumin associated Gd(3+)-complexes have higher relaxivity than the unbound Gd(3+) monochelates. This property appears to be weakly correlated with the lipophilicity of the chelates.
The second class of contrast agents attempts to exploit the anion uptake receptors in the liver as a means of targeting agents to the liver and biliary tract. These compounds are synthesized from cholic acid derivatives. The cholic acid derivatives are modified to have a free primary amine. A DTPA chelate is attached to the free amide via an amide bond to form the bile-salt like contrast agents. MR imaging with these agents demonstrated liver enhancement in rats.
|Rights Information:||Copyright 1994 Marumoto, Alan Kazunari|
|Date Available in IDEALS:||2011-05-07|
|Identifier in Online Catalog:||AAI9416403|