Skip to main content
Log in

Magnetic resonance imaging visualization of targeted cells by the internalization of supramolecular adducts formed between avidin and biotinylated Gd3+ chelates

  • Original Article
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

The high binding affinity between avidin and biotin has been exploited to develop a procedure for magnetic resonance imaging (MRI) visualization of target cells. SHIN3 and PANC1 tumor cell lines have been used as target cells because they possess on their membranes galactosyl receptors able to bind avidin molecules. Avidin–Gd chelate adducts have been built by using two Gd complexes containing one (Gd-I) and two (Gd-II) biotin residues, respectively. The relaxivities of such supramolecular adducts are significantly higher than those shown by free Gd-I and Gd-II. There is evidence of the occurrence of multilayered adducts in which the bis-biotinylated Gd3+ complex acts as a bridge between adjacent avidin molecules. MRI differentiation of labeled versus unlabeled cells has been attained when approximately 6×108 Gd units were internalized in each cell. Furthermore, there is a marked decrease in the measured intracellular T1 relaxivity as the number of internalized Gd complexes increases, probably owing to too short relaxation times of endosomic water protons with respect to their diffusion lifetime.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Rinck PA (1993) Magnetic resonance in medicine. Blackwell, Oxford

    Google Scholar 

  2. Merbach AE, Toth E (2001) Contrast agents in medical magnetic resonance imaging. Wiley, Chichester

    Google Scholar 

  3. Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Chem Rev 99:2293–2352

    Article  Google Scholar 

  4. Weissleder R, Mahmood U (2001) Radiology 219:316–333

    Google Scholar 

  5. Aime S, Cabella C, Colombatto S, Geninatti Crich S, Gianolio E, Maggioni F (2002) J Magn Reson Imaging 16:394–406

    Article  Google Scholar 

  6. Sibson NR, Blamire AM, Bernades-Silva M, Laurent S, Boutry S, Muller RN, Styles P, Anthony DC (2004) Magn Reson Med 51:248–252

    Article  Google Scholar 

  7. Modo M, Mellodew K, Cash D, Fraser SE, Meade TJ, Price J, Williams SCR (2004) Neuroimage 21:311–317

    Article  Google Scholar 

  8. Yao Z, Zhang M, Sakahara H, Saga T, Arano Y, Konishi J (1998) J Natl Cancer Inst 90:25–29

    Article  Google Scholar 

  9. Kobayashi H, Kawamoto S, Saga T, Sato N, Ishimori T, Konishi J, Ono K, Togashi K, Brechbiel MW (2001) Bioconjug Chem 12:587–593

    Article  Google Scholar 

  10. Lotan R, Raz A (1998) Ann N Y Acad Sci 551:385–398

    Google Scholar 

  11. Green NM (1963) Biochem J 89:585–591

    Google Scholar 

  12. Boerman OC, van Schaijk FG, Oyen WJG, Corstens FHM. (2003) J Nucl Med 44:400–411

    PubMed  Google Scholar 

  13. Paganelli G, Bartolomei M, Ferrari M, Cremonesi M, Broggi G, Maira G et al (2001) Cancer Biother Radiopharm 16:227–235

    Google Scholar 

  14. Caliceti P, Chinol M, Roldo M, Veronese FM, Semenzato A, Salmaso S, Paganelli G (2002) J Contr Rel 83:97–108

    Article  Google Scholar 

  15. Sakahara H, Saga T (1999) Adv Drug Deliv Rev 37:89–101

    Google Scholar 

  16. Anelli PL, Fedeli F, Gazzotti O, Lattuada L, Lux G, Rebasti F (1999) Bioconjug Chem 10:137–140

    Google Scholar 

  17. Aime S, Botta M, Fasano M, Terreno E (1998) Chem Soc Rev 27:19–29

    Google Scholar 

  18. Powell DH, Ni Dhubhghaill OH, Pubanz D, Helm L, Lebedev YS, Schlaepfer W, Merbach AE (1996) J Am Chem Soc 118:9333–9346

    Google Scholar 

  19. Botteman F, Nicolle GM, Van der Elst L, Laurent S, Merbach AE, Muller RN (2002) Eur J Inorg Chem 10:2686–2693

    Google Scholar 

  20. Aime S, Botta M, Fasano M, Geninatti Crich S, Terreno E (1996) J Biol Inorg Chem 1:312–319

    Google Scholar 

  21. Green NM, Konieczny L (1971) Biochem J 125:781–791

    Google Scholar 

  22. Wilbur DS, Pathare PM, Hamlin DK, Weerawarna SA (1997) Bioconjugate Chem 8:819–832

    Google Scholar 

  23. Peters JA, Huskens J, Raber DJ (1996) Prog Nuclear Mag Reson Spect 28:283–350

    Google Scholar 

  24. De Stasio G, Casalbore P, Pallini R, Gilbert B, Sanita F, Ciotti MT, Rosi G, Festinesi A, Larocca LM, Rinelli A, Perret D, Mogk DW, Perfetti P, Mehta MP, Mercanti D (2001) Cancer Res 61:4272–4277

    Google Scholar 

  25. Schmalbrock P, Hines JV, Lee SM, Ammar GM, Kwok EW (2001) J Magn Reson Imaging 14:636–648

    Google Scholar 

  26. Geninatti Crich S, Biancone L, Cantaluppi V, Duò D, Esposito G, Russo S, Camussi G, Aime S (2004) Magn Reson Med 51:938–44

    Article  CAS  PubMed  Google Scholar 

  27. Bulte JW, Zhang S, van Gelderen P, Herynek V, Jordan EK, Duncan ID, Frank JA (1999) Proc Natl Acad Sci USA 96:15256–15261

    Google Scholar 

  28. Hoehn M, Kustermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Focking M, Arnold H, Hescheler J, Fleischmann BK, Schwindt W, Buhrle C (2002) Proc Natl Acad Sci USA 99:16267–16272

    Google Scholar 

  29. Billotey C, Wilhelm C, Devaud M, Bacri JC, Bittoun J, Gazeau F (2003) Magn Reson Med 49:646–654

    Google Scholar 

  30. Artemov D, Mori N, Ravi R, Bhujwalla ZM (2003) Cancer Res 63:2723–2727

    Google Scholar 

  31. Winter PM, Caruthers SD, Kassner A, Harris TD, Chinen LK, Allen JS, Lacy EK, Zhang H, Robertson JD, Wickline SA, Lanza GM (2003) Cancer Res 63:5838–5843

    Google Scholar 

  32. Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KC (1998) Nat Med 4:623–626

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by MIUR (PRIN and FIRB). The authors thank Christer Lindqvist (Department of Biology, ABO Akademi University, Abo, Finland) for helpful discussions and Bioindustry Park for the acquisition of magnetic resonance images. Support from Bracco Imaging is gratefully acknowledged.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Silvio Aime.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Geninatti Crich, S., Barge, A., Battistini, E. et al. Magnetic resonance imaging visualization of targeted cells by the internalization of supramolecular adducts formed between avidin and biotinylated Gd3+ chelates. J Biol Inorg Chem 10, 78–86 (2005). https://doi.org/10.1007/s00775-004-0616-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-004-0616-2

Keywords

Navigation