2001 Fiscal Year Final Research Report Summary
Development of Bio-imaging Probes for Morbidity
| Project/Area Number |
11794026
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| Research Category |
Grant-in-Aid for University and Society Collaboration
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| Allocation Type | Single-year Grants |
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| Research Field |
医薬分子機能学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAGANO Tetsuo Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (20111552)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Noriaki Daiichi Chemical Co. Ltd., Synthetic Laboratory, General Manager (Researcher), 素材技術研究所, 所長(研究職)
HIRATA Yasunobu Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 教授 (70167609)
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| Project Period (FY) |
1999 – 2001
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| Keywords | probe / bio-imaging / MRI / zincion / neurotransfer / relaxation / fertilization |
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| Research Abstract |
The MRI image is based upon the NMR signal from the protons of water, and the Signal intensity depends upon the water concentration and relaxation times. Nowadays, there is great interest in MRI contrast agents, which can improve the resolution of MR images. Gadolinium complexes are widely used as contrast agents for MRI.
On the other hand, Zn^<2+> is the second most abundant heavy metal ion after iron in the human body. It is an essential component of many enzymes, transcription factors, and synaptic vesicles in excitatory nerve terminals and is present in serum at a concentration of 〜12 μM (total Zn^<2+>). Recently, Zn^<2+> has been reported to play important roles in regulating synaptic transmission and cell death. Therefore, imaging of chelatable Zn^<2+> in the extra- and intracellular environments or in tissues is of interest. A series of new diethylenetriaminepentaacetic acid (DTPA)-bisamide chelators has been prepared and characterized for application as Zn^<2+> sensors. We have designed and synthesized (GdL)^<2->, which contains a DTPA-bisamide moiety. The R_1 relaxivity of (GdL)^<2-> solution decreased monotonically on the addition of Zn^<2+>. Moreover, (GdL)^<2-> showed high selectivity for Zn^<2+> against Ca^<2+> and Mg^<2+>. These complexes should provide the basis for creating a superior Zn^<2+> sensitive MRI contrast agent and are excellent candidates for incorporation into sensors designed for selective detection of Zn^<2+> in biological applications.
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