5th EuropEan MolEcular IMagIng MEEtIng - ESMI

182
WarSaW, poland May 26 – 29, 2010
P-069 Pyridine-based lanthanide complexes : towards bimodal agents operating as near infrared
luminescent and MRI reporters
Toth E. (1) , Bonnet C. (1) , Villette S. (1) , Suzenet F. (2) , Buron F. (2) , Shade C. (3) , Petoud S. (1) .
(1) Centre de Biophysique Moléculaire, CNRS, Orleans, France
(2) Université d’Orléans, France
(3) University of Pittsburgh, USA
eva.jakabtoth@cnrs-orleans.fr
Introduction: Among the state of the art bioimaging
modalities, some are characterized by high
resolution but low sensitivity (magnetic resonance
imaging, MRI) and others by high sensitivity but
low macroscopic resolution (optical imaging). Luminescent/MRI
bimodal imaging offers the advantage
of combining the high resolution of MRI
with the high sensitivity of luminescence and the
development of contrast agents active for both
techniques is of prime importance. Lanthanides
offer unique opportunity to develop such bimodal
contrast agents given their magnetic and optical
properties. Nevertheless, it was long thought that
the conditions required for both applications were
non-compatible. Here, we report on a versatile pyridine-based
scaffold for Ln 3+ complexation where
MRI and near infrared (NIR) luminescence requirements
are both satisfied using the same ligand.
Methods: The synthesis of the ligands and the complexes
will be briefly described. Potentiometric
titrations have been performed to assess to thermodynamic
stability of the complexes, together
with kinetic measurements to quantify their inertness.
To characterize the MRI properties, the exchange
rate of the water molecules directly bound
the Gd 3+ was determined by measuring 17 O longitudinal
relaxation times. Finally the NIR spectra
of the corresponding Nd 3+ and Yb 3+ were recorded,
as well as the lifetimes of the excited states and the
quantum yield of the complexes to quantify their
luminescent properties.
Results: The bishydrated complexes are found to be
thermodynamically stable and the ligands show a significant
selectivity for Ln 3+ over endogenous cations
such as Zn 2+ , Ca 2+ and Cu 2+ . The kinetic inertness is
also remarkable for such bishydrated complexes. The
chelates do not form ternary complexes with endogenous
donors which does not limit relaxivity in biological
media. All the complexes give rise to NIR emission
and the quantum yields are remarkable. 1 They are in
the same range as those of non-hydrated complexes optimized
for fully protecting the NIR emitting Ln 3+ for
aqueous applications. The modification of the pyridine
into quinoline was successful in shifting the excitation
wavelength of the system towards higher values.
imaging life
Conclusions: The pyridine synthon is a prime candidate
for the development of bimodal NIR/MRI imaging
probes, as the bishydrated Ln 3+ complexes are thermodynamically
and kinetically stable and display a high
NIR quantum yield. The successful modification of the
pyridine into a quinoline did not modify the thermodynamic
properties of the complexes, but it resulted
in a shift of the excitation energy towards lower values
preventing damages to biological samples and allowing
deeper tissue penetration of the excitation photons. The
pyridine platform offers also easy routes for coupling
the probes to biological vectors and optimizing the
MRI properties.
Acknowledgement: This work was financially supported
by the Institut National du Cancer, La Ligue contre
le Cancer, France, and was carried out in the frame of
the COST action D38.
References:
1. L. Pellegatti, J. Zhang, B. Drahos, S. Villette, F. Suzenet,
G. Guillaumet, S. Petoud, E. Toth, Chem. Commun.,
2008, 6591-6593.
2. S. Comby, D. Imbert, C. Vandevyver, J.-C. G. Bünzli,
Chem. Eur. J., 2007, 13, 936.