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Home > Mathematics and Science books > Chemistry > Gadolinium Complexes Containing Polyaminocarboxylate Ligands for the Use of Magnetic Resonance Imaging (MRI) Contrast Agents
Gadolinium Complexes Containing Polyaminocarboxylate Ligands for the Use of Magnetic Resonance Imaging (MRI) Contrast Agents

Gadolinium Complexes Containing Polyaminocarboxylate Ligands for the Use of Magnetic Resonance Imaging (MRI) Contrast Agents


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About the Book

This dissertation, "Gadolinium Complexes Containing Polyaminocarboxylate Ligands for the Use of Magnetic Resonance Imaging (MRI) Contrast Agents" by Wai-yan, Chan, 陳葦恩, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled GADOLINIUM COMPLEXES CONTAINING POLYAMINOCARBOXYLATE LIGANDS FOR THE USE OF MAGNETIC RESONANCE IMAGING (MRI) CONTRAST AGENTS submitted by Chan Wai Yan for the degree of Doctor of Philosophy at The University of Hong Kong in June 2005 The development of contrast agents has an irreplaceable role in elaborating the endless possibilities of Magnetic Resonance Imaging (MRI) as a salient technique in medical diagnosis. In this study, new tailor-made gadolinium complexes were synthesized and investigated with the aim of achieving better medical diagnosis. Three new gadolinium polyaminocarboxylates stem from DTPA-bis(amide) macrocycles, including [Gd(25-DTPA-DOAM)] GdL1, [Gd(26-DTPA-TOAM)] GdL2 and [Gd(16-DTPA-PNAD)] GdL3, were synthesized and well characterized. GdL1 and GdL2 are featured by having ether-linked annular oxygen atoms that bring water molecules to the hydration sphere, while GdL3 has a pendant rigid hydrophobic adamantane moiety that increases specificity. Detailed studies of the relaxometric properties of the complexes using 17 the nuclear magnetic resonance dispersion (NMRD) profiles, variable-temperature O NMR transverse relaxation, pH dependence and temperature dependence relaxivity and luminescence lifetime measurements are discussed. Stability data are obtained from three aspects, the thermodynamic stability by potentiometry; in vivo stability using the rat model provided information on the biodistribution and excretion; and cell assay gives data on toxicity. The three complexes have promising stability, overall neutral charge and one innersphere water molecule. The thermodynamic formation constants (∑logK ) are GdLHn -1 -1 within the range of 20-22. The measured relaxivities are in the order of GdL2 (6.14 mM s ) -1 -1 -1 -1 > GdL3 (5.96 mM s ) > GdL1 (5.87 mM s ) at 20 MHz and 25C. With reference to the clinically approved contrast agents, the new complexes show an average of 30% increase in relaxivity and the thermodynamic stability is comparable to the clinical agents. It is worth mentioning that GdL3 demonstrates excellent liver targeting versus the commercial hepatobiliary agent Gd-BOPTA, and a 23-36 % higher contrast enhancement was found during the 3-hour MRI scan. GdL3 was found to be non-toxic in the in vivo environment and in vitro cell study. Moreover, it is an intracellular agent showing hepatocellular uptake that is an average of 1.97 times larger than that of Gd-BOPTA. The long residence lifetime τ is a major obstacle in attaining high relaxivity for the Gd-based clinical contrast agents. [Gd(DO3Aad)] GdL5 was 1,4,7-tris(acetic acid)-1,4,7,10-tetraazacyclododecnae (DO3A) type ligand designed with a sterically compressed environment to accelerate the water exchange rate and promote relaxivity. The τ was found to be 155 ns (k = 4.1 10 ), which is 1.5 times faster than the clinical agents m ex -1 -1 and is the fastest among the neutral Gd complexes. The relaxivity of GdL5 is 6.14 mM s -1 -1 and its interaction with human serum albumin (HSA) boosts the relaxivity to 18.4 mM s by retarding the reorientational correlation time τ . It has the same adamantane moiety as GdL3, having the liver as the targeting site in the in vivo study. The intensity enhancement is 4 times higher during the delay phase as compared with Gd-BOPTA. The new acyc


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Product Details
  • ISBN-13: 9781361234860
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Height: 279 mm
  • No of Pages: 300
  • Weight: 980 gr
  • ISBN-10: 1361234865
  • Publisher Date: 26 Jan 2017
  • Binding: Hardback
  • Language: English
  • Spine Width: 18 mm
  • Width: 216 mm


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Gadolinium Complexes Containing Polyaminocarboxylate Ligands for the Use of Magnetic Resonance Imaging (MRI) Contrast Agents
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