The synthesis and evaluation of macrocyclic gadolinium-DTPA-bis(amide) complexes as magnetic resonance imaging contrast agents

The authors found that DTPA bis(amide) macrocycles can be prepared in reasonable yields using simple methods and readily available starting materials. Gadolinium complexation is facile and gives rise to monomeric and dimeric species. The "pocket size" influences the solid state structure o...

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Bibliographic Details
Published in:	Investigative radiology Vol. 29 Suppl 2; p. S18
Main Authors:	Varadarajan, J A, Crofts, S P, Carvalho, J F, Fellmann, J D, Kim, S H, Chang, C A, Watson, A D
Format:	Journal Article
Language:	English
Published:	United States 01-06-1994
Subjects:	Animals Contrast Media - chemical synthesis Contrast Media - toxicity Gadolinium DTPA Magnetic Resonance Imaging Mice Molecular Structure Organometallic Compounds - chemical synthesis Organometallic Compounds - toxicity Pentetic Acid - analogs & derivatives Pentetic Acid - chemical synthesis Pentetic Acid - toxicity
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Summary:	The authors found that DTPA bis(amide) macrocycles can be prepared in reasonable yields using simple methods and readily available starting materials. Gadolinium complexation is facile and gives rise to monomeric and dimeric species. The "pocket size" influences the solid state structure of the final complex, with Gd-DTPA-EAM existing as a dimer wherein the macrocycle bridges between two metal centers. Increasing the size of the bridging diamide moiety yields a macrocycle with a sufficiently large pocket to allow for the formation of nine-coordinant monomeric complexes. The solution behavior of all the complexes studied is consistent with the complex being present as monomers. All complexes display kinetic lability comparable to Gd-DTPA-BMA. The measured KTherm and KSel values of the complexes vary with the size of the pocket. Values similar to those observed for Gd-DTPA-BMA have been obtained with Gd-DTPA-OAM. There appears to be a good correlation between log K(Gd/Zn) and the acute toxicity for the complexes studied, with Gd-DTPA-OAM showing a toxicity value similar to that of Gd-DTPA-BMA. Although many of these complexes are chemically interesting, they do not offer any unique advantages as new magnetic resonance imaging contrast agents compared with the DOTA- and DTPA-based products currently used clinically.
ISSN:	0020-9996
DOI:	10.1097/00004424-199406001-00007