Skip to main content
SpringerLink
Log in

Development of 90Y-DOTA-nimotuzumab Fab fragment for radioimmunotherapy

  • Published:
Journal of Radioanalytical and Nuclear Chemistry Aims and scope Submit manuscript

Abstract

Yttrium-90-(90Y) labeled monoclonal antibodies prepared with a chelating agent, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), have been used for radioimmunotherapy of cancer. In the present work, the Fab fragment of anti-EGFR monoclonal antibody nimotuzumab was prepared with high purity, integrity and biological activity. The Fab fragment with high specific recognition of EGFR in NCI-H125 human lung adenocarcinoma cells was derivatized with DOTA-NHS applying a simple procedure. DOTA-nimotuzumab Fab fragment was successfully radiolabeled with 90Y with high radiochemical yield. The in vitro stability of labeled product was optimal over 24 h in buffered solution at 37 °C. Biodistribution and pharmacokinetic studies correctly evaluated the in vivo non-tumor uptake, dosage regimen and excretion pathway in normal Wistar rats.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

References

  1. Boonstra J, Rijken P, Humbel B (1995) Cell Biol Int 19:413–430

    Article  CAS  Google Scholar 

  2. Mateo C, Moreno E, Amour K, Lombardero J, Harris W, Perez R (1997) Immunotechnology 3:71–81

    Article  CAS  Google Scholar 

  3. Crombet T, Casaco A, Iznaga N (2003) Drugs future 28:847–853

    Article  Google Scholar 

  4. Casaco A (2004) Proc Am Soc Clin Oncol 22 Abstract no. 2530

  5. Beckford D, Xiques A, Leyva R, Perez-Malo M, Casanova E, Zamora M (2007) Nucleus 41:3–8

    Google Scholar 

  6. Ondarse D, Leyva R, Zamora M, Ducat L, Hernández I, Alonso LM (2011) Nucleus 49:26–32

    Google Scholar 

  7. Beran M, Beckford D, Forsterova M, Laznickova A, Laznicek M, Melichar F, Leyva R, Barta P (2009) J Label Compd Radiopharm 52:S511

    Google Scholar 

  8. Beckford D, Eigner S, Beran M, Henke KE, Laznickova A, Laznicek M, Melichar F, Chinol M (2011) Cancer Biother Radiopharm 26:287–297

    Article  Google Scholar 

  9. Beckford D, Eigner S, Henke KE, Lebeda O, Melichar F, Beran M (2012) Nucl Med Biol 39:3–13

    Article  Google Scholar 

  10. Calzada V, Zhang X, Fernández M, Díaz A, Iznaga N, Deutscher SL, Balter H, Quinn TP, Cabral PA (2012) Curr Radiopharm 5:318–324

    Article  CAS  Google Scholar 

  11. Grünberg J, Novak I, Honer M (2005) Clin Cancer Res 11:5112–5120

    Article  Google Scholar 

  12. Parham P (1983) J Immunol 131:2895–2902

    CAS  Google Scholar 

  13. Laemmli UK (1970) Nature 227:680–685

    Article  CAS  Google Scholar 

  14. Lewis MR, Raubitschek A, Shively JE (1994) Bioconjug Chem 5:565–576

    Article  CAS  Google Scholar 

  15. Xiques A, Isaac K, Casanova E, Beckford D, Leyva R, Montero A, Olive E (2009) Radiochim Acta 97:739

    Google Scholar 

  16. Sakahara H, Endo K, Nakashima T, Koizumi M, Ohta H, Torizuka K, Furukawa T, Ohmomo Y, Okada K, Yoshida O, Nishi S (1985) J Nucl Med 26:750–755

    CAS  Google Scholar 

  17. Tikhomirov I, Garrido G, Rabasa A, Perez R (2009) Ann Oncol 20:III32–III35

    Google Scholar 

  18. Salomon DS, Brandt R, Ciardiello F, Normanno N (1995) Crit Rev Oncol Hematol 19:83–232

    Article  Google Scholar 

  19. Parham P (1986) In: Wier DM (ed) Handbook of experimental immunology: immunochemistry. Blackwell Scientific, London

    Google Scholar 

  20. Parham P (1983) J Immunol 131:2895–2902

    CAS  Google Scholar 

  21. Behr TM, Sharkey RM, Sgouros G (1997) Cancer 80:2591–2610

    Article  CAS  Google Scholar 

  22. Zimmermann K, Gianollini S, Schubiger PA, Novak-Hofer I (1999) Nucl Med Biol 26:943–950

    Article  CAS  Google Scholar 

  23. Kim I, Kobayashi H, Yoo TM (2002) Nucl Med Biol 29:795–801

    Article  CAS  Google Scholar 

  24. Behr TM, Sharkey RM, Juweid ME, Blumenthal RD, Dunn RM, Griffiths GL, Bair HJ, Wolf FG, Becker WS, Goldenberg DM (1995) Cancer Res 55:3825–3834

    CAS  Google Scholar 

  25. Chapman AP (2002) Adv Drug Deliv Rev 54:531–545

    Article  CAS  Google Scholar 

  26. Meibohm B (2006) Pharmacokinetics and pharmacodynamics of biotech drugs. Wiley, Germany

    Book  Google Scholar 

  27. Iznaga N, Morales A, Duconge J, Caballero I, Fernández E, Gomez JA (1998) Nucl Med Biol 25:17–23

    Article  Google Scholar 

  28. Beckford D, Eigner S, Eigner KH, Leyva R, Melichar F, Beran M (2013) Results Cancer Res 194:301–317

    Article  Google Scholar 

  29. Covell DG, Barbet J, Holton OD (1986) Cancer Res 46:3969–3978

    CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the Center of Molecular Immunology for their kind support. Funding of this work was partially provided by the International Atomic Energy Agency through the co-ordinated research project on “Development of Generator Technologies for Therapeutic Radionuclides: 90Y and 188Re”.

Author information

Authors and Affiliations

  1. Deparment of Radiopharmacy, Center of Isotopes, Ave Monumental y Carr. La Rada, Km 3½, 22, Guanabacoa, Havana, Cuba

    Luis M. Alonso Martínez, Abmel Xiques Castillo, Marylaine Pérez-Malo Cruz & René Leyva Montaña

  2. Jubilant DraxImage, 16751 Trans-Canada Highway, Kirkland, QC, H9H 4J4, Canada

    Abmel Xiques Castillo

  3. Centro de Investigaciones Nucleares, Universidad de la República, Mataojo 2055, 11400, Montevideo, Montevideo, Uruguay

    Victoria N. Calzada Falcón

  4. Deparment of Quality Control, Center of Isotopes, Ave Monumental y Carr. La Rada, Km 3½, 22, Guanabacoa, Havana, Cuba

    Minely Zamora Barrabí & Alejandro Arbesú Valdivia

  5. Deparment of Development, Center of Isotopes, Ave Monumental y Carr. La Rada, Km 3½, 22, Guanabacoa, Havana, Cuba

    Ignacio Hernández González & Mariela León Pérez

Authors
  1. Luis M. Alonso Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abmel Xiques Castillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victoria N. Calzada Falcón
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marylaine Pérez-Malo Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. René Leyva Montaña
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Minely Zamora Barrabí
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ignacio Hernández González
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mariela León Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alejandro Arbesú Valdivia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luis M. Alonso Martínez.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alonso Martínez, L.M., Xiques Castillo, A., Calzada Falcón, V.N. et al. Development of 90Y-DOTA-nimotuzumab Fab fragment for radioimmunotherapy. J Radioanal Nucl Chem 302, 49–56 (2014). https://doi.org/10.1007/s10967-014-3402-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-014-3402-9

Keywords

Search

Navigation