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

Rivas, Charlotte; Stasiuk, Graeme J.; Gallo, Juan; Minuzzi, Florencia; Rutter, Guy A.; Long, Nicholas J.

Abstract

Two novel dual-modal MRI/optical probes based on a rhodamine-DO3A conjugate have been prepared. The bis aqua-Gd(III) complex Gd.L1 and mono aqua-Gd(III) complex Gd.L2 behave as dual-modal imaging probes (r1 = 8.5 and 3.8 mM-1s-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 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 HEK cells. Co-localisation with MitoTracker® Green confirmed that Gd.L2 compartmentalizes in the mitochondria. Gd.L2 was also evaluated as an MRI probe for imaging tumors in BALB/c nude mice bearing M21 xenografts. A 36.5% decrease in T1 within the tumor was observed 30 minutes 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 micro-environment of tumor cells.

Citation

Rivas, C., Stasiuk, G. J., Gallo, J., Minuzzi, F., Rutter, G. A., & Long, N. J. (2013). Lanthanide(III) complexes of rhodamine-DO3A conjugates as agents for dual-modal imaging. Inorganic chemistry, 52(24), 14284-14293. https://doi.org/10.1021/ic402233g

• Journal Article Type: Article
• Acceptance Date: Sep 2, 2013
• Online Publication Date: Dec 4, 2013
• Publication Date: Dec 16, 2013
• Deposit Date: Feb 23, 2016
• Publicly Available Date: Feb 23, 2016
• Journal: Inorganic chemistry
• Print ISSN: 0020-1669
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 52
• Issue: 24
• Pages: 14284-14293
• DOI: https://doi.org/10.1021/ic402233g
• Keywords: Dual mode imaging, Magnetic resonance imaging, Fluorescence, Rhodamine, Lanthanides
• Public URL: https://hull-repository.worktribe.com/output/411136
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/ic402233g
• Additional Information: This is a copy of an article published in Inorganic chemistry, 2013, v.52 issue 24.
• Contract Date: Feb 23, 2016