RGD-Peptide Functionalization Affects the <i>In Vivo</i> Diffusion of a Responsive Trimeric MRI Contrast Agent through Interactions with Integrins

The relevance of
MRI as a diagnostic methodology has been expanding
significantly with the development of molecular imaging. Partially,
the credit for this advancement is due to the increasing potential
and performance of targeted MRI contrast agents, which are able to
specifically bind distinct receptors or biomarkers. Consequently,
these allow for the identification of tissues undergoing a disease,
resulting in the over- or underexpression of the particular molecular
targets. Here we report a multimeric molecular probe, which combines
the established targeting properties of the Arg-Gly-Asp (RGD) peptide
sequence toward the integrins with three calcium-responsive, Gd-based
paramagnetic moieties. The bifunctional probe showed excellent 1H MRI contrast enhancement upon Ca2+ coordination
and demonstrated a longer retention time in the tissue due to the
presence of the RGD moiety. The obtained results testify to the potential
of combining bioresponsive contrast agents with targeting vectors
to develop novel functional molecular imaging methods.