| Co-Investigator(Kenkyū-buntansha) |
URANO Yasuteru The University of Tokyo, Graduate School of Pharmaceutical Sciences, Associate Professor (20292956)
KOJIMA Hirotatsu The University of Tokyo, Associate Professor (70345255)
HIRATA Yasunobu The University of Tokyo, Graduate School of Medicine, Associate Professor (70167609)
KIKUCHI Kazuya Osaka University, Graduate School of Engineering, Professor (70292951)
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| Research Abstract |
The aim of this project is to develop bioimaging probes for application in vivo. Bioimaging technique is an essential method for elucidating biological phenomena in living cells, slice tissues or in vivo. Luminescent lanthanide complexes, such as europium and terbium trivalent ions (Eu^<3+> and Tb^<3+>) complexes, have various experimental advantages, including a large Stoke's shift (>150 nm), high water solubility and long luminescence lifetime of the order of milliseconds, allowing measurements to be made after the decay of short-lived background fluorescence, in contrast to typical organic fluorescent dyes, which possess short fluorescence lifetimes in the nanosecond region. In this project, we developed various luminescent Eu^<3+> complexes for the application to time-resolved long-lived luminescence microscopy (TRLLM), to demonstrate that appropriate properties for TRLLM can be attained by the design of a suitable sensitizing chromophore in lanthanide complexes. The TRLLM images w
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ere used to monitor intracellular Zn^<2+> concentrations changes with [Eu-7], and dual-color time-resolved long-lived luminescence images were also obtained by using both luminescent Eu^<3>+ and Tb^<3+> complexes. Furthermore, MRI contrast agents, which can improve the resolution of MR images, have attracted much attention. Gadolinium (Gd^<3+>) complexes are commonly used as MRI contrast agents, and Gd^<3+> primarily enhances the T_1 (spin-lattice) relaxation rates of water protons by rapid exchange of inner-sphere water molecules with bulk solvent. The highly specific imaging of gene expression is one of desirable goals in this project. β-Galactosidase has been used for decades as a marker to monitor gene expression. There are some reports on β-galactosidase-activated MRI contrast agents so far. However, a range of β-galactosidase-activated MRI contrast agents with various chemical properties (e. g., different reactivity for β-galactosidase, different biodistribution in living specimens, and different magnitude of change in the MR signal in response to β-galactosidase activity.) is needed for further biological studies. Our approach for this purpose is due to the receptor-induced magnetization enhancement (RIME). We developed a new β-galactosidase-activated MRI contrast agent based on the RIME approach. This novel β-galactosidase-activated MRI contrast agent, based on the RIME phenomenon, should be an excellent candidate for incorporation into sensors for MRI, for selective detection of β-galactosidase activity in biological systems. Less
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