Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Gadolinium Complexes of Bifunctional Diethylenetriaminepentaacetic Acid (DTPA)-bis(amides) as Copper Responsive Smart Magnetic Resonance Imaging Contrast Agents (MRI CAs)

  • Nam, Ki Soo (Department of Applied Chemistry, Kyungpook National University) ;
  • Park, Ji-Ae (Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences) ;
  • Jung, Ki-Hye (Department of Applied Chemistry, Kyungpook National University) ;
  • Chang, Yongmin (Department of Medical & Biological Engineering, Kyungpook National University) ;
  • Kim, Tae-Jeong (Department of Applied Chemistry, Kyungpook National University)
  • Received : 2013.06.10
  • Accepted : 2013.07.04
  • Published : 2013.10.20
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Abstract

We present the synthesis and characterization of DTPA-bis(histidylamide) (1a), DTPA-bis(aspartamide) (1b), and their gadolinium complexes of the type $[Gd(L)(H_2O)]$ (2a:L = 1a; 2b:L = 1b). Thermodynamic stabilities and $R_1$ relaxivities of 2a-b compare well with Omniscan$^{(R)}$, a well-known commercial, extracellular (ECF) MRI CA which adopts the DTPA-bis(amide) framework for the chelate: $R_1$ = 5.5 and 5.1 $mM^{-1}$ for 2a and 2b, respectively. Addition of the Cu(II) ion to a solution containing 2b triggers relaxivity enhancement to raise $R_1$ as high as 15.3 $mM^{-1}$, which corresponds to a 300% enhancement. Such an increase levels off at the concentration beyond two equiv. of Cu(II), suggesting the formation of a trimetallic ($Gd/Cu_2$) complex in situ. Such a relaxivity increase is almost negligible with Zn(II) and other endogenous ions such as Na(I), K(I), Mg(II), and Ca(II). In vivo MR images and the signal-to-noise ratio (SNR) obtained with an aqueous mixture of 2b and Cu(II) ion in an 1:2 ratio demonstrate the potentiality of 2 as a copper responsive MRI CA.

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References

  1. Caravan, P. Chem. Soc. Rev. 2006, 35, 512. https://doi.org/10.1039/b510982p
  2. Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer, R. B. Chem. Rev. 1999, 99, 2293. https://doi.org/10.1021/cr980440x
  3. Aime, S.; Dastru, W.; Crich, S. G.; Gianolio, E.; Mainero, V. Biopolym. 2002, 66, 419. https://doi.org/10.1002/bip.10357
  4. Caravan, P. Acc. Chem. Res. 2009, 42, 851. https://doi.org/10.1021/ar800220p
  5. Caravan, P.; Zhang, Z. Eur. J. Inorg. Chem. 2012, 2012, 1916. https://doi.org/10.1002/ejic.201101364
  6. Geraldes, C. F.; Laurent, S. Contrast Media Mol. Imaging 2009, 4, 1. https://doi.org/10.1002/cmmi.265
  7. Henrotte, V.; Vander Elst, L.; Laurent, S.; Muller, R. N. J. Biol. Inorg. Chem. 2007, 12, 929. https://doi.org/10.1007/s00775-007-0247-5
  8. Jacques, V.; Desreux, J. F. Top. Curr. Chem. 2002, 221, 123. https://doi.org/10.1007/3-540-45733-X_5
  9. Lattuada, L.; Barge, A.; Cravotto, G.; Giovenzana, G. B.; Tei, L. Chem. Soc. Rev. 2011, 40, 3019. https://doi.org/10.1039/c0cs00199f
  10. Clark, R. B. Top. Curr. Chem. 2002, 221.
  11. Schmitt-Willich, H.; Brehm, M.; Ewers, C. L. J.; Michl, G.; Muller-Fahrnow, A.; Petrov, O.; Platzek, J.; Raduchel, B.; Sulzle, D. Inorg. Chem. 1999, 38.
  12. Uggeri, F.; Aime, S.; Botta, P. L. A. M.; Brocchetta, J. M.; Ermondi, C. d. H. G.; GrandiJ, M.; Paolio, P. Inorg. Chem. 1995.
  13. Aime, S.; Botta, M.; Garino, E.; Crich, S. G.; Giovenzana, G.; Pagliarin, R.; Palmisano, G.; Sisti, M. Chem.-Eur. J. 2000, 6, 2609. https://doi.org/10.1002/1521-3765(20000717)6:14<2609::AID-CHEM2609>3.0.CO;2-S
  14. Chong, H. S.; Song, H. A.; Ma, X.; Lim, S.; Sun, X.; Mhaske, S. B. Chem. Commun. 2009, 3011.
  15. Barrio, J. R.; Satyamurthy, N.; Huang, S.-C.; Petri, A.; Small, G. W.; Kepe, V. Acc. Chem. Res. 2009, 42, 842. https://doi.org/10.1021/ar800189x
  16. Tweedle, M. F. Acc. Chem. Res. 2009, 42, 958. https://doi.org/10.1021/ar800215p
  17. Giovenzana, G. B.; Negri, R.; Rolla, G. A.; Tei, L. Eur. J. Inorg. Chem. 2012, 2012, 2035. https://doi.org/10.1002/ejic.201101296
  18. Angelovski, G.; Fouskova, P.; Mamedov, I.; Canals, S.; Toth, E.; Logothetis, N. K. Chembiochem. 2008, 9, 1729. https://doi.org/10.1002/cbic.200800165
  19. Mishra, A.; Fouskova, P.; Angelovski, G.; Balogh, E.; Mishra, A. K.; Logothetis, N. K.; Toth, E. Inog. Chem. 2008, 47, 1370. https://doi.org/10.1021/ic7017456
  20. Dhingra, K.; Fouskova, P.; Angelovski, G.; Maier, M. E.; Logothetis, N. K.; Toth, E. J. Biol. Inorg. Chem. 2008, 13, 35.
  21. Dhingra, K.; Maier, M. E.; Beyerlein, M.; Angelovski, G.; Logothetis, N. K. Chem. Commun. 2008, 3444.
  22. Hanaoka, K.; Kikuchi, K.; Urano, Y.; Nagano, T. J. Chem. Soc. Perkin Trans. 2 2001, 1840.
  23. Major, J. L.; Parigi, G.; Luchinat, C.; Meade, T. J. Proc. Natl. Acad. Acad. Sci. U. S. A. 2007, 104, 13881. https://doi.org/10.1073/pnas.0706247104
  24. Major, J. L.; Boiteau, R. M.; Meade, T. J. Inog. Chem. 2008, 47, 10788. https://doi.org/10.1021/ic801458u
  25. Hanaoka, K.; Kikuchi, K.; Urano, Y.; Narazaki, M.; Yokawa, T.; Sakamoto, S.; Yamaguchi, K.; Nagano, T. Chem. Biol. 2002, 9, 1027. https://doi.org/10.1016/S1074-5521(02)00216-8
  26. Trokowski, R.; Ren, J.; Kalman, F. K.; Sherry, A. D. Angew. Chem., Int. Ed. 2005, 44, 6920. https://doi.org/10.1002/anie.200502173
  27. Li, W.-h.; Parigi, G.; Fragai, M.; Luchinat, C.; Meade, T. J. Inog. Chem. 2002, 41, 4018. https://doi.org/10.1021/ic0200390
  28. Li, W.-h.; Fraser, S. E.; Meade, T. J. J. Am. Chem. Soc. 1999, 121, 1413. https://doi.org/10.1021/ja983702l
  29. Zhang, X.-a.; Lovejoy, K. S.; Jasanoff, A.; Lippard, S. J. Proc. Natl. Acad. Sci. USA. 2007, 104, 10780. https://doi.org/10.1073/pnas.0702393104
  30. Nivorozhkin, A. L.; Kolodziej, A. F.; Caravan, P.; Greenfield, M. T.; Lauffer, R. B.; McMurry, T. J. Angew. Chem., Int. Ed. 2001, 40, 2903. https://doi.org/10.1002/1521-3773(20010803)40:15<2903::AID-ANIE2903>3.0.CO;2-N
  31. Zhao, M.; Josephson, L.; Tang, Y.; Weissleder, R. Angew. Chem., Int. Ed. 2003, 42, 1375. https://doi.org/10.1002/anie.200390352
  32. Moats, R. A.; Fraser, S. E.; Meade, T. J. Angew. Chem., Int. Ed. 1997, 36, 725.
  33. Duimstra, J. A.; Femia, F. J.; Meade, T. J. J. Am. Chem. Soc. 2005, 127, 12847. https://doi.org/10.1021/ja042162r
  34. Yoo, B.; Pagel, M. D. J. Am. Chem. Soc. 2006, 128, 14032. https://doi.org/10.1021/ja063874f
  35. Mizukami, S.; Takikawa, R.; Sugihara, F.; Hori, Y.; Tochio, H.; lchli, M. W.; Shirakawa, M.; Kikuchi, K. J. Am. Chem. Soc. 2008, 130, 794. https://doi.org/10.1021/ja077058z
  36. Louie, A. Y.; Huber, M. M.; Ahrens, E. T.; Rothbacher, U.; Moats, R.; Jacobs, R. E.; Fraser, S. E.; Meade, T. J. Nature Biotech. 2000, 18, 321. https://doi.org/10.1038/73780
  37. Querol, M.; Chen, J. W.; Weissleder, R.; Alexei Bogdanov, J. Org. Lett. 2005, 7, 1719. https://doi.org/10.1021/ol050208v
  38. Chauvin, T.; Durand, P.; Bernier, M.; Meudal, H.; Doan, B. T.; Noury, F.; Badet, B.; Beloeil, J. C.; Toth, E. Angew. Chem. Int. Ed. 2008, 47, 4370. https://doi.org/10.1002/anie.200800809
  39. Giardiello, M.; Lowe, M. P.; Botta, M. Chem. Commun. 2007, 4044.
  40. Hanaoka, K.; Kikuchi, K.; Terai, T.; Komatsu, T.; Nagano, T. Chem.-Eur. J. 2008, 14, 987. https://doi.org/10.1002/chem.200700785
  41. Zhang, S.; Trokowski, R.; Sherry, A. D. J. Am. Chem. Soc. 2003, 125, 15288. https://doi.org/10.1021/ja038345f
  42. Trokowski, R.; Zhang, S.; Sherry, A. D. Bioconjug Chem. 2004, 15, 1431. https://doi.org/10.1021/bc0498976
  43. Park, J.-A.; Kim, J. Y.; Kim, H.-K.; Lee, W.; Lim, S. M.; Chang, Y.; Kim, T.-J.; Kim, K. M. ACS. Med. Chem. Lett. 2012, 3, 299. https://doi.org/10.1021/ml200285p
  44. Jung, K. H.; Kim, H. K.; Lee, G. H.; Kang, D. S.; Park, J. A.; Kim, K. M.; Chang, Y. M.; Kim, T. J. J. Med. Chem. 2011, 54, 5385. https://doi.org/10.1021/jm2002052
  45. Que, E. L.; Chang, C. J. Chem. Soc. Rev. 2010, 39, 51. https://doi.org/10.1039/b914348n
  46. Que, E. L.; Domaille, D. W.; Chang, C. J. Chem. Rev. 2008, 108, 1517. https://doi.org/10.1021/cr078203u
  47. Que, E. L.; Gianolio, E.; Baker, S. L.; Aimec, S.; Chang, C. J. Dalton Trans. 2010, 39, 469. https://doi.org/10.1039/b916931h
  48. Que, E. L.; Gianolio, E.; Baker, S. L.; Wong, A. P.; Aime, S.; Chang, C. J. J. Am. Chem. Soc. 2009, 131, 8527. https://doi.org/10.1021/ja900884j
  49. Viguier, R. F. H.; Hulme, A. N. J. Am. Chem. Soc. 2006, 128, 11370. https://doi.org/10.1021/ja064232v
  50. Zeng, L.; Miller, E. W.; Pralle, A.; Isacoff, E. Y.; Chang, C. J. J. Am. Chem. Soc. 2006, 128, 10. https://doi.org/10.1021/ja055064u
  51. Gu, S.; Kim, H. K.; Lee, G. H.; Kang, B. S.; Chang, Y.; Kim, T. J. J. Med. Chem. 2011, 54, 143. https://doi.org/10.1021/jm100966t

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