Open AccessImproving T 1 and T 2 magnetic resonance imaging contrast agents through the conjugation of an esteramide dendrimer to high‐water‐coordination Gd(III) hydroxypyridinone complexes
Author(s) -
Klemm Piper J.,
Floyd William C.,
Smiles Danil E.,
Fréchet Jean M. J.,
Raymond Kenneth N.
Publication year - 2012
Publication title -
contrast media & molecular imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.714
H-Index - 50
eISSN - 1555-4317
pISSN - 1555-4309
DOI - 10.1002/cmmi.483
Subject(s) - dendrimer , gadolinium , chemistry , molecule , mri contrast agent , aqueous solution , small molecule , magnetic resonance imaging , macromolecule , relaxation (psychology) , conjugated system , covalent bond , nuclear magnetic resonance , combinatorial chemistry , polymer , polymer chemistry , organic chemistry , biochemistry , radiology , medicine , physics , psychology , social psychology
Commercial gadolinium magnetic resonance imaging (MRI) contrast agents are limited by low relaxivity ( r 1 ) and coordination to only a single water molecule ( q = 1). Consequently, gram quantities of these agents must be injected to obtain sufficient diagnostic contrast. In this study, MRI contrast agents for T 1 and T 2 relaxivity were synthesized using hydroxypyridinone and terephthalamide chelators with mesityl and 1,4,7‐triazacyclononane capping moieties. When covalently conjugated to a highly biocompatible esteramide dendrimer, T 2 relaxation rates up to 52 m m −1 s −1 and T 1 relaxation rates up to 31 m m −1 s −1 per gadolinium were observed under clinically relevant conditions. These values are believed to be brought about by using a dendritic macromolecule to decrease the molecular tumbling time of the small molecule complexes. These agents also show high aqueous solubility and low toxicity in vitro . In this study we report six new compounds: three discrete complexes and three dendrimer conjugates. Copyright © 2012 John Wiley & Sons, Ltd.