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Oral 24
Abstract
Using Relaxometry to Probe the Traditional SBM Paradigm
Mark Woods <strong>and</strong> Mauro Botta
Department of Chemistry, Portl<strong>and</strong> State University; Advanced Imaging Research Center,
Oregon Health <strong>and</strong> Science University; Dipartimento di Scienze e Innovazione Tecnologica,
Università del Piemonte Orientale "A. Avogadro"
It is now well established the relaxivity of Gd 3+ chelates is relatively well described
by Solomon Bloembergen <strong>and</strong> Morgan theory. This in turn informs our underst<strong>and</strong>ing of the
limitations on relaxivity of the low molecular
weight Gd 3+ chelates used in clinical practice.
These agents tumble rapidly in solution which
limits their relaxivity. When this rotational
restriction is lifted by making the chelates tumble
more slowly the relaxivity continues to be limited
by the slower than optimal water exchange
kinetics of the chelate. Thus it has been widely
understood that in order to maximize relaxivity it
is necessary to both slow molecular tumbling <strong>and</strong>
optimize water exchange. This concept is often
represented graphically in the manner shown in
Figure 1.
Figure 1. A simulation of relaxivity as
function of molecular tumbling <strong>and</strong> water
exchange.
To probe the potential gains in relaxivity that can be achieved through the
optimization of water exchange kinetics we prepared two isomeric chelates of a Gd 3+ DOTA
derivative. The two chelates were designed to tumble slowly (similar R ) <strong>and</strong> were known to
possess very similar electron spin relaxation characteristics ( 2 <strong>and</strong> V ). The primary
difference between the two chelates was the water exchange rate: one was very fast the other
somewhat slower. According to established
theory the more rapidly exchanging isomer
( M = 8 ns) should afford the highest
relaxivity. However, relaxometric studies of
both isomers in various slowly tumbling
systems have revealed that in fact the more
slowly exchanging isomer ( M = 70 ns) affords
the highest relaxivity (Figure 2). Significantly
the relaxometric data affords <strong>and</strong> insight it
why this unexpected result should be the case:
Figure 2. High field 1 H NMRD profiles of
the fast (closed circles) <strong>and</strong> slow (open
diamonds) exchanging isomers.
there is a difference in the hydration state
(q/r 6 ) between the two chelates which limits
relaxivity in the most rapidly exchanging
isomer.
<strong>8th</strong> <strong>Conference</strong> on Fast Field Cycling NMR Relaxometry, Turin 23-25 May 2013