Title

具有偵測銅金屬離子之8-hydroxyquinoline衍生物磁振造影對比劑

Translated Titles

A new gadolinium(III) complex with 8-hydroxyquinoline based ligand as a copper sensor for MRI

DOI

10.6842/NCTU.2011.00721

Authors

江宗憲

Key Words

磁振造影 ; 銅離子 ; MRI ; copper

PublicationName

交通大學生物科技學系學位論文

Volume or Term/Year and Month of Publication

2011年

Academic Degree Category

碩士

Advisor

王雲銘

Content Language

繁體中文

Chinese Abstract

過去幾年來越來越多的證據顯示腦內的金屬離子不平衡會導致許多疾病。由於磁振造影(MRI)具有非侵入性及高解析度之優點,使磁振造影成為臨床醫療診斷上相當重要之影像工具。且磁振造影之對比劑也愈來愈被重視,各種不同功能之對比劑也漸漸被開發。在本研究中,設計並合成可偵測細胞中二價銅離子之磁振造影對比劑[Gd(HQ-DO3A)]。在銅離子存在的環境下,[Gd(HQ-DO3A)]的內層水分子數及弛緩率有顯著上升。除此之外,[Gd(HQ-DO3A)]與其他金屬離子比較對於銅離子也有良好的選擇性。另一方面,當Cu2+ 存在時,因為Cu2+會削弱quinolin之螢光,使得原先由quinolin轉移至銪金屬(Eu3+)之能量減少,進而使銪金屬(Eu3+)所發出之螢光也被削弱。由結果顯示[Gd(HQ-DO3A)]相當具有潛力可成為利用磁振造影來偵測二價銅離子之雙功能磁振造影對比劑。

English Abstract

Over the past few years, more and more evidence indicated that the metal ion imbalance in the brain will give rise to many diseases. Magnetic resonance imaging (MRI) is a non-invasive and high resolution technique that has become a powerful diagnostic tool in medicine. In this study, we have developed a new contrast agent [Gd(HQ-DO3A)] that can recognize Cu2+ ion in the cells. The significant increases in the relaxivity (r1) and hydration number (q) in the present of Cu2+ were observed. Moreover, the Gd3+ complex attributes excellent selectivity for Cu2+ over a choice of other metal ions. A gradual increase was shown in the signal enhancement of MR imaging upon copper ion detection. On the other hand, we observed fluorescence intensity decreased via transferring the inner system energy from qunoline ring to Eu3+ when copper was absent. These results implicate that a new MR based contrast agent can serve as a Cu2+ sensor using MR imaging.

Topic Category 生物科技學院 > 生物科技學系暨研究所
生物農學 > 生物科學
Reference
  1. 2. Werner, E. J.; Datta A.; Jocher, C. J. and Raymond, K. N., Angew. Chem. Int. Ed., 2008, 47, 8568- 8580.
    連結:
  2. 3. Runge, V. M.; Foster, M. A.; Clanton, J. A.; Jones, M. M.; Lukehart, C. M.; Hutchison, J. M.; Mallard, J. R.; Smith, F.W.; Partain, C. L. and James, A. E. Jr., Radiology, 1984, 152, 123- 126.
    連結:
  3. 6. The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging, ed. Merbach, A. E., Toth, E., Wiley, J. and Sons, C. 2001.
    連結:
  4. 10. Ehnebom, L.; Fjaertoft, P. B. Acta Chem. Scand., 1992, 46, 126-135.
    連結:
  5. 11. Ou, M. H.; Tu, C. H.; Tsai, S. C.; Lee, W. T.; Liu, G. C.; Wang, Y. M. Inorg. Chem., 2006, 45, 244-254.
    連結:
  6. 12. Chang, Y. H.; Chen, C.Y.; Singh, G.; Chen, H.Y.; Liu, G.C.; Goan, Y.G., Aime, S. and Wang, Y. M., Inorg.Chem., 2011, 50, 1275-1287.
    連結:
  7. 13. Frullano, L.; Catana, C.; Benner, T.; Sherry, A. D. and Caravan, P. Angew. Chem. Int. Ed., 2010, 49, 2382-2384.
    連結:
  8. 14. Tu, C.; Nagao, R. and Louie, A. Y., Angew. Chem. Int. Ed., 2009, 48, 6547 -6551.
    連結:
  9. 18. Youn, J. H. and McDonough, A. A., Annu. Rev. Physiol., 2009, 71, 381-401.
    連結:
  10. 20. Frederickson, C. J.; Koh, J. Y. and Bush, A. I., Nat. Rev. Neurosci., 2005, 6, 449-462.
    連結:
  11. 21. Hanaoka, K., Kikuchi, K., Urano, Y. and Nagano, T., J. Chem. Soc., Perk. Trans., 2001, 2, 1840-1843.
    連結:
  12. 23. Que, E. L. and Chang, C. J., J. Am .Chem. Soc. 2006, 128, 15942-15943.
    連結:
  13. 24. Kasala, D.; Lin, T. S.; Chen, C. Y.; Liu, G. C.; Kao, C. L.; Cheng, T. L. and Wang, Y. M., Dalton Trans., 2011, 40, 5018-5025.
    連結:
  14. 25. Beeby, A. and Woods, M., J. Chem. Soc., Perkin Trans. 1999, 493-504.
    連結:
  15. 26. Horrocks, W. DeW., Jr. and Sudnick, D. R., J. Am. Chem. Soc. 1979, 101, 334-340.
    連結:
  16. 1. Caravan, P. ; Ellison, J. J.; McMurry, T. J. and Lauffer, R. B., Chem.Rev., 1999, 9, 2293- 2352.
  17. 4. Weinmann, H.J.; Brasch, R. C.; Press, W. R. and Wesbey, G. E., Am. J. Roentgenol., 1984, 142, 619- 624.
  18. 5. Idée, J. M.; Port, M.; Raynal, I.; Schaefer, M.; Greneur, S. and Corot, C., Fundam Clin Pharmacol., 2006, 20, 563-76.
  19. 7. Hermann, P.; Kotek, J.; Kubicek, V. and Luke, I., Dalton Trans., 2008, 23, 3017-3124.
  20. 8. Aime, S.; Botta, M.; Fasano, M. and Terreno, E., Chem. Soc. Rev., 1998, 27, 19-29.
  21. 9. Gries, H. and Miklautz, H., Physiol. Chem. Phys. Med. NMR., 1984, 16, 105-112.
  22. 15. Lin, Y. H.; Dayananda, K.; Chen, C. Y.; Liu, G. C.; Luo, T. Y.; Hsu, H. S. and Wang, Y. M., Bioorg. Med. Chem., 2010, 19, 1085-1096.
  23. 16. Berridge, M. J.; Lipp, P. and Bootman, M. D., Nat. Rev. Mol. Cell Biol., 2000, 1, 11- 21.
  24. 17. Dhingra, K.; Maier, M. E.; Beyerlein, M.; Angelovski, G. and Logothetis, N. K., Chem. Commun., 2008, 29, 3444-3446.
  25. 19. Hifumi, H.; Tanimoto, A.; Citterio, D.; Komatsu, H. and Suzuki, K., Analyst., 2007, 132, 1153-1160.
  26. 22. Parac-Vogt, T. N.; Vander, L.; Kimpe, K.; Laurent, S.; Burtéa, C.; Chen, F.; Van, R.; Ni, Y.; Muller, R. N. and Binnemans, K., Contrast Media Mol. Imaging., 2006, 1, 267-278.
  27. 27. Ciesienski, K. L.; Hyman, L. M.; Derisavifard, S. and Franz, K. J., Inorg. Chem., 2010, 49, 6808–6810