Lanthanide(III) complexes of rhodamine-DO3A conjugates as agents for dual-modal imaging

TY - JOUR

T1 - Lanthanide(III) complexes of rhodamine-DO3A conjugates as agents for dual-modal imaging

AU - Rivas, Charlotte

AU - Stasiuk, Graeme J.

AU - Gallo, Juan

AU - Minuzzi, Florencia

AU - Rutter, Guy A.

AU - Long, Nicholas J.

PY - 2013/12/16

Y1 - 2013/12/16

N2 - Two novel dual-modal MRI/optical probes based on a rhodamine-DO3A conjugate have been prepared. The bis(aqua)gadolinium(III) complex Gd.L1 and mono(aqua)gadolinium(III) complex Gd.L2 behave as dual-modal imaging probes (r1 = 8.5 and 3.8 mM-1 s-1 for Gd.L1 and Gd.L2, respectively; λex = 560 nm and λem = 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 Tb(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 Gd.L2 in HEK293 cells and primary mouse islet cells (∼70% insulin-containing β cells). Colocalization with MitoTracker Green demonstrated Gd.L2's ability to distinguish between tumor and healthy cells, with compartmentalization believed to be in the mitochondria. Gd.L2 was also evaluated as an MRI probe for imaging of tumors in BALB/c nude mice bearing M21 xenografts. A 36.5% decrease in T1 within the tumor was observed 30 min post injection, showing that Gd.L2 is preferentially up taken in the tumor. Gd.L2 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.

AB - Two novel dual-modal MRI/optical probes based on a rhodamine-DO3A conjugate have been prepared. The bis(aqua)gadolinium(III) complex Gd.L1 and mono(aqua)gadolinium(III) complex Gd.L2 behave as dual-modal imaging probes (r1 = 8.5 and 3.8 mM-1 s-1 for Gd.L1 and Gd.L2, respectively; λex = 560 nm and λem = 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 Tb(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 Gd.L2 in HEK293 cells and primary mouse islet cells (∼70% insulin-containing β cells). Colocalization with MitoTracker Green demonstrated Gd.L2's ability to distinguish between tumor and healthy cells, with compartmentalization believed to be in the mitochondria. Gd.L2 was also evaluated as an MRI probe for imaging of tumors in BALB/c nude mice bearing M21 xenografts. A 36.5% decrease in T1 within the tumor was observed 30 min post injection, showing that Gd.L2 is preferentially up taken in the tumor. Gd.L2 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.

UR - http://www.scopus.com/inward/record.url?scp=84890739576&partnerID=8YFLogxK

U2 - 10.1021/ic402233g

DO - 10.1021/ic402233g

M3 - Article

C2 - 24304423

AN - SCOPUS:84890739576

SN - 0020-1669

VL - 52

SP - 14284

EP - 14293

JO - INORGANIC CHEMISTRY

JF - INORGANIC CHEMISTRY

IS - 24

ER -