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Design and evaluation of gadolinium(...

Werner, Eric Joseph.

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Design and evaluation of gadolinium(III) complexes as high-relaxivity MRI contrast agents.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Design and evaluation of gadolinium(III) complexes as high-relaxivity MRI contrast agents./
Author:	Werner, Eric Joseph.
Description:	203 p.
Notes:	Adviser: Kenneth N. Raymond.
Contained By:	Dissertation Abstracts International68-08B.
Subject:	Chemistry, Inorganic. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3275648
ISBN:	9780549173250

Design and evaluation of gadolinium(III) complexes as high-relaxivity MRI contrast agents.
Werner, Eric Joseph.

Design and evaluation of gadolinium(III) complexes as high-relaxivity MRI contrast agents. - 203 p.

Adviser: Kenneth N. Raymond.

Thesis (Ph.D.)--University of California, Berkeley, 2007.

The emergence of new instrumentation and applications for Magnetic Resonance Imaging (MRI) invites the development of more efficient contrast agents. Current commercial agents employ gadolinium(III) complexes of polyaminocarboxylate ligands and achieve modest relaxivities (increase in water proton longitudinal relaxation) due to a low number of coordinated water molecules (q = 1) and slow water exchange rates. Raymond and coworkers (University of California, Berkeley) have developed a family of stable hydroxypyridinone (HOPO)-based Gd(III) chelates that show promise as next-generation contrast agents due to an increased hydration number and faster water exchange rates leading to relaxivities that are about twice the values for commercial agents. A unique aspect of these compounds is that, unlike what is observed for currently used clinical agents, the relaxivity does not typically decrease with increasing magnetic field strength (e.g. 3 T).

ISBN: 9780549173250Subjects--Topical Terms:

517253
Chemistry, Inorganic.

Design and evaluation of gadolinium(III) complexes as high-relaxivity MRI contrast agents.
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020 $a 9780549173250
035 $a (UMI)AAI3275648
035 $a AAI3275648
040 $a UMI $c UMI
100 1 $a Werner, Eric Joseph. $3 1285809
245 1 0 $a Design and evaluation of gadolinium(III) complexes as high-relaxivity MRI contrast agents.
300 $a 203 p.
500 $a Adviser: Kenneth N. Raymond.
500 $a Source: Dissertation Abstracts International, Volume: 68-08, Section: B, page: 5233.
502 $a Thesis (Ph.D.)--University of California, Berkeley, 2007.
520 $a The emergence of new instrumentation and applications for Magnetic Resonance Imaging (MRI) invites the development of more efficient contrast agents. Current commercial agents employ gadolinium(III) complexes of polyaminocarboxylate ligands and achieve modest relaxivities (increase in water proton longitudinal relaxation) due to a low number of coordinated water molecules (q = 1) and slow water exchange rates. Raymond and coworkers (University of California, Berkeley) have developed a family of stable hydroxypyridinone (HOPO)-based Gd(III) chelates that show promise as next-generation contrast agents due to an increased hydration number and faster water exchange rates leading to relaxivities that are about twice the values for commercial agents. A unique aspect of these compounds is that, unlike what is observed for currently used clinical agents, the relaxivity does not typically decrease with increasing magnetic field strength (e.g. 3 T).
520 $a Work reported herein probes the water coordination and exchange properties of Gd(III) complexes in the HOPO ligand system. The goal is to achieve high relaxivity at high field, and this is pursued through variation of the ligand platform in an attempt to increase the number of inner-sphere waters (higher q) and optimize their exchange rate. The 1,2-HOPO isomer was explored in both tris and heteropodal ligand architectures to probe the effect of a more acidic ligand on water exchange. As predicted, these complexes possess extremely high exchange rates (tauM = 2 ns), and their high stability demonstrates the viability of such agents for clinical use. New ligand scaffolds for Gd-HOPO complexes based on mesityl (ME) and triazacyclononane (TACN) structures were also investigated. Preliminary relaxivities of the ME-capped complexes were high (e.g. 23 mM-1s-1, 20 MHz), but low solubility motivated further analysis of more soluble derivatives. Unique pH dependent relaxivities were then observed due to the unexpected formation of large aggregates in solution with reduced q and slow rotation. Finally, stable q = 3 complexes were achieved for the TACN-capped chelates. This high hydration number combined with high aqueous solubility, fast water exchange, and slow electronic relaxation makes these compounds promising as high-relaxivity agents for future MRI applications ( r1p &sim; 14 mM-1 s-1, 60 MHz).
590 $a School code: 0028.
650 4 $a Chemistry, Inorganic. $3 517253
690 $a 0488
710 2 $a University of California, Berkeley. $3 687832
773 0 $t Dissertation Abstracts International $g 68-08B.
790 $a 0028
790 1 0 $a Raymond, Kenneth N., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3275648