2010 Fiscal Year Final Research Report
Design and synthesis of MRI contrast agents and their biological applications
| Project/Area Number |
20689001
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HANAOKA Kenjiro The University of Tokyo, 大学院・薬学系研究科, 講師 (70451854)
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| Project Period (FY) |
2008 – 2010
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| Keywords | MRI / 蛍光 / イメージング / ランタノイド / マルチモーダルイメージング |
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| Research Abstract |
Gadolinium ion (Gd^<3+>) complexes are commonly used as magnetic resonance imaging (MRI) contrast agents to enhance signals in T1-weighted MR images. Most MRI contrast agents are mainly extracellular agents with nonspecific biodistribution. However, it is also possible to develop Gd^<3+> complexes with various chemical properties by means of appropriate ligand design for Gd^<3+>. In this research, we have developed a novel method to achieve functional Gd^<3+> complexes by using hydrophobic fluorescent dyes as a cell-permeability-enhancing unit and a targeting moiety for atherosclerotic plaques. i.e., we have synthesized Gd^<3+> complexes conjugated with various hydrophobic fluorescent dyes, and showed that these conjugates could be introduced efficiently into cells. Moreover, we have designed and synthesized novel MRI contrast agents by combining Gd^<3+> complexes and boron dipyrromethene (BDP) derivatives, and have successfully visualized atherosclerotic plaques of ApoE^<-/-> mice by MRI. Thus, conjugation of hydrophobic fluorescent dyes appears to be an effective approach to control the functions of Gd^<3+> complexes, and should be applicable for further development of functional Gd^<3+>-based MRI contrast agents.
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