1 research outputs found
Lanthanide(III) Complexes of Rhodamine–DO3A Conjugates as Agents for Dual-Modal Imaging
Two
novel dual-modal MRI/optical probes based on a rhodamine–DO3A
conjugate have been prepared. The bisÂ(aqua)ÂgadoliniumÂ(III) complex <b>Gd.L1</b> and monoÂ(aqua)ÂgadoliniumÂ(III) complex <b>Gd.L2</b> behave as dual-modal imaging probes (<i>r</i><sub>1</sub> = 8.5 and 3.8 mM<sup>–1</sup> s<sup>–1</sup> for <b>Gd.L1</b> and <b>Gd.L2</b>, respectively; λ<sub>ex</sub> = 560 nm and λ<sub>em</sub> = 580 nm for both complexes).
The rhodamine fragment is pH-sensitive, and upon lowering of the pH,
an increase in fluorescence intensity is observed as the spirolactam
ring opens to give the highly fluorescent form of the molecule. The
ligands are bimodal when coordinated to TbÂ(III) ions, inducing fluorescence
from both the lanthanide center and the rhodamine fluorophore, on
two independent time frames. Confocal imaging experiments were carried
out to establish the localization of <b>Gd.L2</b> in HEK293
cells and primary mouse islet cells (∼70% insulin-containing
β cells). Colocalization with MitoTracker Green demonstrated <b>Gd.L2</b>’s ability to distinguish between tumor and healthy
cells, with compartmentalization believed to be in the mitochondria. <b>Gd.L2</b> was also evaluated as an MRI probe for imaging of tumors
in BALB/c nude mice bearing M21 xenografts. A 36.5% decrease in <i>T</i><sub>1</sub> within the tumor was observed 30 min post
injection, showing that <b>Gd.L2</b> is preferentially up taken
in the tumor. <b>Gd.L2</b> is the first small-molecule MR/fluorescent
dual-modal imaging agent to display an off–on pH switch upon
its preferential uptake within the more acidic microenvironment of
tumor cells