Physical Sciences and Mathematics Commons^™

Human Whole-Blood (1)H2o Longitudinal Relaxation With Normal And High-Relaxivity Contrast Reagents: Influence Of Trans-Cell-Membrane Water Exchange, Gregory J. Wilson, Mark Woods, Charles S. Springer Jr., Sarah Bastawrous, Puneet Bhargava, Jeffrey H. Maki

Chemistry Faculty Publications and Presentations

PURPOSE: Accurate characterization of contrast reagent (CR) longitudinal relaxivity in whole blood is required to predict arterial signal intensity in contrast-enhanced MR angiography (CE-MRA). This study measured the longitudinal relaxation rate constants (R₁ ) over a concentration range for non-protein-binding and protein-binding CRs in ex vivo whole blood and plasma at 1.5 and 3.0 Tesla (T) under physiologic arterial conditions.

METHODS: Relaxivities of gadoteridol, gadobutrol, gadobenate, and gadofosveset were measured for [CR] from 0 to 18 mM [mmol(CR)/L(blood)]: the latter being the upper limit of what may be expected in CE-MRA.

RESULTS: In plasma, the ¹H2 O R …

Coupling Fast Water Exchange To Slow Molecular Tumbling In Gd3+ Chelates: Why Faster Is Not Always Better, Stefano Avedano, Mauro Botta, Julian Saunders Haigh, Dario L. Lango, Mark Woods

Chemistry Faculty Publications and Presentations

The influence of dynamics on solution state structure is a widely overlooked consideration in chemistry. Variations in Gd³⁺ chelate hydration with changing coordination geometry and dissociative water exchange kinetics substantially impact the effectiveness (or relaxivity) of monohydrated Gd³⁺ chelates as T1-shortening contrast agents for MRI. Theory shows that relaxivity is highly dependent upon the Gd³⁺–water proton distance (rGdH), and yet this distance is almost never considered as a variable in assessing the relaxivity of a Gd³⁺ chelate as a potential contrast agent. The consequence of this omission can be seen when considering …

Cest And Paracest Mr Contrast Agents, Ileana Hancu, W. Thomas Dixon, Mark Woods, Elena Vinogradov, A. Dean Sherry, Robert E. Lenkinski

Chemistry Faculty Publications and Presentations

In this review we describe the status of development for a new class of magnetic resonance (MR) contrast agents, based on chemical exchange saturation transfer (CEST). The mathematics and physics relevant to the description of the CEST effect in MR are presented in an appendix published in the online version only. We discuss the issues arising when translating in vitro results obtained with CEST agents to using these MR agents in in vivo model studies and in humans. Examples are given on how these agents are imaged in vivo. We summarize the status of development of these CEST agents, and …

A Bridge To Coordination Isomer Selection In Lanthanide(Iii) Dota-Tetraamide Complexes, Jeff Vipond, Mark Woods, Piyu Zhao, Gyula Tircsó, Jimin Ren, Simon G. Bott, Doug Ogrin, Garry Kiefer, Zoltan Kovacs, A. Dean Sherry

Chemistry Faculty Publications and Presentations

Interest in macrocyclic lanthanide complexes such as DOTA is driven largely through interest in their use as contrast agents for MRI. The lanthanide tetraamide derivatives of DOTA have shown considerable promise as PARACEST agents, taking advantage of the slow water exchange kinetics of this class of complex. We postulated that water exchange in these tetraamide complexes could be slowed even further by introducing a group to sterically encumber the space above the water coordination site, thereby hindering the departure and approach of water molecules to the complex. The ligand 8O₂-bridged-DOTAM was synthesized in a 34% yield from cyclen. …

Toward The Design Of Mr Agents For Imaging Β-Cell Function, Mark Woods, Shanrong Zhang, A. Dean Sherry

Chemistry Faculty Publications and Presentations

The chemistry of Gd3+-based MRI agents has advanced considerably during the past decade toward agents with higher relaxivity and agents that respond to physiology and / or metabolism. This review describes various approaches that have been taken toward the development of responsive contrast agents and discusses the importance of fast water exchange for advancement of targeted Gd3+-based agents with higher sensitivity. The recent discovery of Eu3+ complexes having extraordinarily slow water exchange has opened a new avenue in contrast agent design based upon the chemical exchange saturation transfer (CEST) mechanism. These new paramagnetic complexes called PARACEST agents offer new possibilities …