Lanthanide(III) Complexes of Rhodamine鈥揇O3A Conjugates as Agents for Dual-Modal Imaging

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• 作者：Charlotte Rivas ; Graeme J. Stasiuk ; Juan Gallo ; Florencia Minuzzi ; Guy A. Rutter ; Nicholas J. Long
• 刊名：Inorganic Chemistry
• 出版年：2013
• 出版时间：December 16, 2013
• 年：2013
• 卷：52
• 期：24
• 页码：14284-14293
• 全文大小：535K
• 年卷期：v.52,no.24(December 16, 2013)
• ISSN：1520-510X

文摘

Two novel dual-modal MRI/optical probes based on a rhodamine鈥揇O3A 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^鈥? s^鈥? for Gd.L1 and Gd.L2, respectively; 位_ex = 560 nm and 位_em = 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 尾 cells). Colocalization with MitoTracker Green demonstrated Gd.L2鈥檚 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鈥搊n pH switch upon its preferential uptake within the more acidic microenvironment of tumor cells.