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Abstract

Magnetic resonance imaging (MRI) is currently
one of the most powerful tools in medical
diagnosis and is strongly related to the development of paramagnetic contrast agents. These are
commonly based on trivalent gadolinium which has the
strong influence on the relaxation of surrounding
water protons.
The objective of our study is to develop a MRI-d
etectable molecule for tracking the modulation
in calcium, which is an excellent marker tightly linked to brain activation. Recently, our group
synthesized and investigated the properties of several Ca-sensitive, smart contrast agents (SCA) [1,2].
Using a different approach than previously reporte
d, we prepared a new series of potential DO3A-based
SCAs, having alkylaminobis(methylenephosphonate) side
chains. Four different ligands with propyl,
butyl, pentyl or hexyl linkers between the aminobi
s(methylenephosphonates) and DO3A were prepared
and the physico-chemical properties of their Gd(III) and
Eu(III) complexes were studied.
Significant differences were observed
in the longitudinal relaxivity (
r
1
) response of studied
Gd(III)-complexes towards Ca(II) being dependant on th
e aliphatic side chain length. No changes in
r
1
of
the propyl analogue were found over the whole span
of Ca(II) concentration whereas the decrease to 61%
of the initial
r
1
value was observed for the complex bearing hexyl linker.
Additional studies, including various NMR and luminescence spectroscopy methods, were
performed on these systems in order to understand th
eir unusual behavior. The results indicate very
unique coordination properties of these complexes
leading to a specific triggering mechanism
responsible for the
r
1
changes. These findings will be helpful fo
r future design of novel SCA classes, as
well as for their application in MRI.