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.
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References
Rinck PA (1993) Magnetic resonance in medicine. Blackwell, Oxford
Merbach AE, Toth E (2001) Contrast agents in medical magnetic resonance imaging. Wiley, Chichester
Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Chem Rev 99:2293–2352
Weissleder R, Mahmood U (2001) Radiology 219:316–333
Aime S, Cabella C, Colombatto S, Geninatti Crich S, Gianolio E, Maggioni F (2002) J Magn Reson Imaging 16:394–406
Sibson NR, Blamire AM, Bernades-Silva M, Laurent S, Boutry S, Muller RN, Styles P, Anthony DC (2004) Magn Reson Med 51:248–252
Modo M, Mellodew K, Cash D, Fraser SE, Meade TJ, Price J, Williams SCR (2004) Neuroimage 21:311–317
Yao Z, Zhang M, Sakahara H, Saga T, Arano Y, Konishi J (1998) J Natl Cancer Inst 90:25–29
Kobayashi H, Kawamoto S, Saga T, Sato N, Ishimori T, Konishi J, Ono K, Togashi K, Brechbiel MW (2001) Bioconjug Chem 12:587–593
Lotan R, Raz A (1998) Ann N Y Acad Sci 551:385–398
Green NM (1963) Biochem J 89:585–591
Boerman OC, van Schaijk FG, Oyen WJG, Corstens FHM. (2003) J Nucl Med 44:400–411
Paganelli G, Bartolomei M, Ferrari M, Cremonesi M, Broggi G, Maira G et al (2001) Cancer Biother Radiopharm 16:227–235
Caliceti P, Chinol M, Roldo M, Veronese FM, Semenzato A, Salmaso S, Paganelli G (2002) J Contr Rel 83:97–108
Sakahara H, Saga T (1999) Adv Drug Deliv Rev 37:89–101
Anelli PL, Fedeli F, Gazzotti O, Lattuada L, Lux G, Rebasti F (1999) Bioconjug Chem 10:137–140
Aime S, Botta M, Fasano M, Terreno E (1998) Chem Soc Rev 27:19–29
Powell DH, Ni Dhubhghaill OH, Pubanz D, Helm L, Lebedev YS, Schlaepfer W, Merbach AE (1996) J Am Chem Soc 118:9333–9346
Botteman F, Nicolle GM, Van der Elst L, Laurent S, Merbach AE, Muller RN (2002) Eur J Inorg Chem 10:2686–2693
Aime S, Botta M, Fasano M, Geninatti Crich S, Terreno E (1996) J Biol Inorg Chem 1:312–319
Green NM, Konieczny L (1971) Biochem J 125:781–791
Wilbur DS, Pathare PM, Hamlin DK, Weerawarna SA (1997) Bioconjugate Chem 8:819–832
Peters JA, Huskens J, Raber DJ (1996) Prog Nuclear Mag Reson Spect 28:283–350
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
Schmalbrock P, Hines JV, Lee SM, Ammar GM, Kwok EW (2001) J Magn Reson Imaging 14:636–648
Geninatti Crich S, Biancone L, Cantaluppi V, Duò D, Esposito G, Russo S, Camussi G, Aime S (2004) Magn Reson Med 51:938–44
Bulte JW, Zhang S, van Gelderen P, Herynek V, Jordan EK, Duncan ID, Frank JA (1999) Proc Natl Acad Sci USA 96:15256–15261
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
Billotey C, Wilhelm C, Devaud M, Bacri JC, Bittoun J, Gazeau F (2003) Magn Reson Med 49:646–654
Artemov D, Mori N, Ravi R, Bhujwalla ZM (2003) Cancer Res 63:2723–2727
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
Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KC (1998) Nat Med 4:623–626
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.
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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
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DOI: https://doi.org/10.1007/s00775-004-0616-2