The Chemistry of Lanthanide MRI Contrast Agents - The Chemistry of Molecular Imaging - page 195

increases in relaxivity, with the binding of bicarbonate to the Ca.gd adduct perturbing the equilibrium. given the speed of
modern instrumentation, these responsive agents have potential to track changes in ion concentrations within the brain.
Meade and co-workers have established the use of enzyme dependent contrast agents such as that shown in Figure 8.10
[95, 96]. In this case, a galactose unit is attached to a dO3A derivative via an acetal link. The bulk of this substituent and its
capacity as an O-donor ligand restricts access by water to the gadolinium site, resulting in a low relaxivity. However, galac-
tosidase selectively cleaves the acetal, giving rise to an increase in q and a concomitant increase in relaxivity. This allows
such a probe to be used to assess galactosidase concentration (provided the concentration of the probe can be established by
other means).

8.7 concLusIons and prospects

Magnetic resonance imaging has already made a dramatic contribution to human well-being, even though clinical agents are
currently devoted to imaging blood pool. Over the last decade, significant contributions to the field have raised the prospect
of extending the use of such systems to other forms of diagnosis and analysis. The examples given in the text above are just
that: Many groups are working toward extending the effectiveness of gadolinium-containing contrast media. In theory, the
maximum contrast achievable could be as high as 350 mmolgd -1 s -1 ; such high values would raise the prospect of effective
receptor targeting, combined with low dose for more conventional contrast measurements.
We have seen how it is beginning to be possible to control the relaxivity through design that influences molecular size and
tumbling, close approach of water and the rate of water exchange, and through electronic relaxation properties of coordi-
nated gadolinium. This last point represents an area in which immediate progress toward understanding and quantifying the
electronic relaxation time is both possible and desirable. Studies on self-assembled and multimeric systems have revealed
alternative strategies for maximising relaxivity: These also need further development before clinical application.
Perhaps the key to progress is the development of new generation techniques for quantitative imaging that combine the best
that synthetic chemistry and data analysis have to offer with new approaches to developing instrumentation. With these in place,
the future for gadolinium contrast agents looks rosy. Alternative strategies to MRI imaging are discussed elsewhere in this volume.

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