Book of Abstracts - Ruhr-Universität Bochum

P-56
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Novel MRI Contrast Agents based on a Silsesquioxane Core
Jörg Henig, a,b* É. Jakab-Tóth, c J. Engelmann, d S. Gottschalk, d H.A. Mayer a
a Universität Tübingen, Institut für Anorganische Chemie, Auf der Morgenstelle 18, 72076 Tübingen,
Germany. b Ruhr-Universität Bochum, Zentrum für Elektrochemie, Universitätsstraße 150, 44801
Bochum, Germany. c CNRS Orléans, Le Centre de Biophysique Moléculaire, 45071 Orléans, France.
d Max-Planck-Institut für biologische Kybernetik, Hochfeld-Magnetresonanz-Zentrum, 72076
Tübingen, Germany. E-mail: joerg.henig@rub.de
Large macromolecular MRI contrast agents (CAs) bearing several paramagnetic gadolinium(III)
centres show usually significantly higher relaxivities than small size CAs and are particularly useful
for target specific imaging. However, the large size slows down the excretion rate of the CA, which is
a major limitation for clinical use. Furthermore, the Solomon-Bloembergen-Morgan theory predicts
that at the high magnetic fields of modern clinical and especially research MRI scanners, medium-size
CAs rather than very large systems are the most favored in order to achieve high relaxivities. Here we
present two novel medium-size CAs (Gadoxane G (GG) and Gadoxane B (GB), Figure 1), based on a
symmetric T8-silsesquioxane core. The use of the T8-silsesquioxane cube allows the grafting of eight
monohydrated lanthanide (Ln = Gd 3+ , Y 3+ ) complexes in a confined space.
Both Gadoxanes can be synthesised with an intact silsesquioxane core. Diffusion 1 H NMR
measurements showed rotational correlation times of about 3.35 ns for both compounds. Even though
both CAs have almost identical water exchange rates, due to the lower internal flexibility, the
longitudinal relaxivities of GB are significantly higher than those of GG over almost the whole range
of magnetic fields. Although both systems still possess a high internal flexibility, the strong effect of
the altered spacer on the relaxivity and the comparatively high relaxivity of both systems at proton
Larmor frequencies above 100 MHz points out the potential of moderate-size silsesquioxane-based
CAs. Furthermore, with hydrodynamic radii of about 1.44 nm both, GG and GB are still significantly
smaller than the small pores of the glomerular filtration system and hence should be excreted
relatively fast via the kidneys. A key feature is also the lability of the silsesquioxane cage under
physiological conditions (37°C, pH 7.4). No change in relaxivity is observed within the first three
hours, since the hydrolysis of the initial Si-O-Si moieties has no influence on rotational correlation
time. However, then the hydrolysis of the silsesquioxane core leads to smaller fragments and therefore
to a decrease in relaxivity. If needed, this degradation might allow the development of larger CAs,
whose fragments are then readily excreted via the kidneys.
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Figure 1. Gadoxane G (GG) and Gadoxane B (GB)
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