Advertisement

Preparation and evaluation of 89Zr-Zevalin for monitoring of 90Y-Zevalin biodistribution with positron emission tomography

  • Lars R. Perk
  • Otto J. Visser
  • M. Stigter-van Walsum
  • Maria J. W. D. Vosjan
  • Gerard W. M. Visser
  • Josée M. Zijlstra
  • Peter C. Huijgens
  • Guus A. M. S. van DongenEmail author
Original article

Abstract

Purpose

To evaluate whether 89Zr can be used as a PET surrogate label for quantification of 90Y-ibritumomab tiuxetan (90Y-Zevalin) biodistribution and dosimetry before myeloablative radioimmunotherapy.

Methods

Zevalin was labelled with 89Zr by introducing N-succinyldesferal (N-sucDf) as a second chelate. For comparison of the in vitro stability of 89Zr-Zevalin and 88Y-Zevalin (as a substitute for 90Y), samples were incubated in human serum at 37°C up to 6 days. Biodistribution of 89Zr-Zevalin and 88Y-Zevalin was assessed at 24, 48, 72 and 144 h p.i. by co-injection in nude mice bearing the non-Hodgkin’s lymphoma (NHL) xenograft line Ramos. The clinical performance of 89Zr-Zevalin-PET was evaluated via a pilot imaging study in a patient with NHL, who had undergone [18F]FDG-PET 2 weeks previously.

Results

Modification of Zevalin with N-sucDf resulted in an N-sucDf-to-antibody molar ratio of 0.83±0.04. After radiolabelling and purification, the radiochemical purity and immunoreactivity of 89Zr-Zevalin always exceeded 95% and 80%, respectively. 89Zr-Zevalin showed the same stability in serum as 88Y-Zevalin, with a radiochemical purity >95% during a period of 6 days. The co-injected 89Zr-Zevalin and 88Y-Zevalin conjugates showed a very similar biodistribution, except for liver and bone accumulation at 72 and 144 h p.i., which was significantly higher for 89Zr than for 88Y. PET images obtained after injection of 89Zr-Zevalin showed clear targeting of all known tumour lesions.

Conclusion

89Zr-Zevalin and 88Y-Zevalin showed a very similar biodistribution in mice, implying that 89Zr-Zevalin-PET might be well suited for prediction of 90Y-Zevalin biodistribution in a myeloablative setting.

Keywords

Immuno-PET Radioimmunotherapy Ibritumomab tiuxetan Zirconium-89 Yttrium-90 

Notes

Acknowledgements

This project was financially supported by the Dutch Technology Foundation (STW, grant VBC.6120). The authors thank Schering Nederland BV (The Netherlands) for supply of Zevalin and for reviewing the manuscript, the technical staff of BV Cyclotron and the Radionuclide Centre for supply and processing of 89Zr, Jan H. Rector (Solid State Physics, VU university) for sputtering 89Y on copper supports, Adriaan A. Lammertsma for providing PET imaging facilities, and Yvonne W.S. Jauw and Ronald Boellaard for performing PET reconstructions.

References

  1. 1.
    Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol 2002;20:2453–2463PubMedCrossRefGoogle Scholar
  2. 2.
    Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol 2002;20:3262–3269PubMedCrossRefGoogle Scholar
  3. 3.
    Hagenbeek A, Lewington V. Report of a European consensus workshop to develop recommendations for the optimal use of 90Y-ibritumomab tiuxetan (Zevalin) in lymphoma. Ann Oncol 2005;16:786–792PubMedCrossRefGoogle Scholar
  4. 4.
    Winter JN. Combining yttrium 90-labeled ibritumomab tiuxetan with high-dose chemotherapy and stem cell support in patients with relapsed non-Hodgkin’s lymphoma. Clin Lymphoma 2004;5 Suppl 1:22–26CrossRefGoogle Scholar
  5. 5.
    Nademanee A, Forman S, Molina A, Fung H, Smith D, Dagis A, et al. A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma. Blood 2005;106:2896–2902PubMedCrossRefGoogle Scholar
  6. 6.
    Verel I, Visser GWM, van Dongen GAMS. The promise of immuno-PET in radioimmunotherapy. J Nucl Med 2005;46 Suppl 1:164–171Google Scholar
  7. 7.
    Pauwels S, Barone R, Walrand S, Borson-Chazot F, Valkema R, Kvols LK, et al. Practical dosimetry of peptide receptor radionuclide therapy with 90Y-labeled somatostatin analogs. J Nucl Med 2005;46 Suppl 1:92–98Google Scholar
  8. 8.
    Lövqvist A, Humm JL, Sheikh A, Finn RD, Koziorowski J, Ruan S, et al. PET imaging of 86Y-labeled anti-Lewis Y monoclonal antibodies in a nude mouse model: comparison between 86Y and 111In radiolabels. J Nucl Med 2001;42:1281–1287PubMedGoogle Scholar
  9. 9.
    Verel I, Visser GWM, Boellaard R, Stigter-Van Walsum M, Snow GB, Van Dongen GAMS. Zr-89 immuno-PET: comprehensive procedures for the production of Zr-89-labeled monoclonal antibodies. J Nucl Med 2003;44:1271–1281PubMedGoogle Scholar
  10. 10.
    Verel I, Visser GWM, Boellaard R, Boerman OC, Van Eerd J, Snow GB, et al. Quantitative Zr-89 immuno-PET for in vivo scouting of Y-90-labeled monoclonal antibodies in xenograft-bearing nude mice. J Nucl Med 2003;44:1663–1670PubMedGoogle Scholar
  11. 11.
    Lindmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA. Determination of the immunoreactive fraction of radiolabeled monoclonal-antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods 1984;72:77–89PubMedCrossRefGoogle Scholar
  12. 12.
    Zijlstra JM, Hoekstra OS, Raijmakers PGHM, Comans EFI, van der Hoeven JJM, Teule GJJ, et al. 18FDG positron emission tomography versus 67Ga scintigraphy as prognostic test during chemotherapy for non-Hodgkin’s lymphoma. Br J Haematol 2003;123:454–462PubMedCrossRefGoogle Scholar
  13. 13.
    Perk LR, Visser GWM, Vosjan MJWD, Stigter-van Walsum M, Tijink BM, Leemans CR, et al. 89Zr as a PET surrogate radioisotope for scouting biodistribution of the therapeutic radiometals 90Y and 177Lu in tumor-bearing nude mice after coupling to the internalizing antibody cetuximab. J Nucl Med 2005;46:1898–1906PubMedGoogle Scholar
  14. 14.
    Verel I, Visser GWM, Boerman OC, Van Eerd JEM, Finn R, Boellaard R, et al. Long-lived positron emitters zirconium-89 and iodine-124 for scouting of therapeutic radioimmunoconjugates with PET. Cancer Biother Radiopharm 2003;18:655–661PubMedCrossRefGoogle Scholar
  15. 15.
    van Gog FB, Visser GWM, Klok R, van der Schors R, Snow GB, van Dongen GAMS. Monoclonal antibodies labeled with rhenium-186 using the MAG3 chelate: relationship between the number of chelated groups and biodistribution characteristics. J Nucl Med 1996;37:352–362PubMedGoogle Scholar
  16. 16.
    van Gog FB, Visser GWM, Stroomer JWG, Roos JC, Snow GB, van Dongen GAMS. High dose rhenium-186-labeling of monoclonal antibodies for clinical application: pitfalls and solutions. Cancer 1997;80:2360–2370PubMedCrossRefGoogle Scholar
  17. 17.
    Chinn PC, Leonard JE, Rosenberg J, Hanna N, Anderson DR. Preclinical evaluation of 90Y-labeled anti-CD20 monoclonal antibody for treatment of non-Hodgkin’s lymphoma. Int J Oncol 1999;15:1017–1025PubMedGoogle Scholar
  18. 18.
    Camera L, Kinuya S, Garmestani K, Brechbiel MW, Wu C, Pai LH, et al. Comparative biodistribution of indium- and yttrium-labeled B3 monoclonal antibody conjugated to either 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M-DTPA) or 2-(p-SCN-Bz)-1,4,7,10-tetraazacyclododecane tetraacetic acid (2B-DOTA). Eur J Nucl Med 1994;21:640–646PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Lars R. Perk
    • 1
  • Otto J. Visser
    • 2
  • M. Stigter-van Walsum
    • 1
  • Maria J. W. D. Vosjan
    • 1
  • Gerard W. M. Visser
    • 3
  • Josée M. Zijlstra
    • 2
    • 3
  • Peter C. Huijgens
    • 2
  • Guus A. M. S. van Dongen
    • 1
    • 3
    Email author
  1. 1.Department of Otolaryngology/Head and Neck SurgeryVU University Medical CentreAmsterdamThe Netherlands
  2. 2.Department of HematologyVU University Medical CentreAmsterdamThe Netherlands
  3. 3.Department of Nuclear Medicine and PET ResearchVU University Medical CentreAmsterdamThe Netherlands

Personalised recommendations