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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 11/2006

01.11.2006 | Original article

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

verfasst von: 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 Dongen

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 11/2006

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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.
Literatur
1.
Zurück zum Zitat 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;20:2453–2463PubMedCrossRef 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;20:2453–2463PubMedCrossRef
2.
Zurück zum Zitat 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;20:3262–3269PubMedCrossRef 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;20:3262–3269PubMedCrossRef
3.
Zurück zum Zitat 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;16:786–792PubMedCrossRef 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;16:786–792PubMedCrossRef
4.
Zurück zum Zitat 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 1:22–26CrossRef 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 1:22–26CrossRef
5.
Zurück zum Zitat 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;106:2896–2902PubMedCrossRef 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;106:2896–2902PubMedCrossRef
6.
Zurück zum Zitat Verel I, Visser GWM, van Dongen GAMS. The promise of immuno-PET in radioimmunotherapy. J Nucl Med 2005;46 Suppl 1:164–171 Verel I, Visser GWM, van Dongen GAMS. The promise of immuno-PET in radioimmunotherapy. J Nucl Med 2005;46 Suppl 1:164–171
7.
Zurück zum Zitat 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 1:92–98 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 1:92–98
8.
Zurück zum Zitat 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;42:1281–1287PubMed 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;42:1281–1287PubMed
9.
Zurück zum Zitat 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;44:1271–1281PubMed 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;44:1271–1281PubMed
10.
Zurück zum Zitat 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;44:1663–1670PubMed 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;44:1663–1670PubMed
11.
Zurück zum Zitat 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;72:77–89PubMedCrossRef 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;72:77–89PubMedCrossRef
12.
Zurück zum Zitat 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;123:454–462PubMedCrossRef 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;123:454–462PubMedCrossRef
13.
Zurück zum Zitat 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;46:1898–1906PubMed 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;46:1898–1906PubMed
14.
Zurück zum Zitat 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;18:655–661PubMedCrossRef 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;18:655–661PubMedCrossRef
15.
Zurück zum Zitat 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;37:352–362PubMed 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;37:352–362PubMed
16.
Zurück zum Zitat 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;80:2360–2370PubMedCrossRef 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;80:2360–2370PubMedCrossRef
17.
Zurück zum Zitat 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;15:1017–1025PubMed 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;15:1017–1025PubMed
18.
Zurück zum Zitat 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;21:640–646PubMedCrossRef 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;21:640–646PubMedCrossRef
Metadaten
Titel
Preparation and evaluation of 89Zr-Zevalin for monitoring of 90Y-Zevalin biodistribution with positron emission tomography
verfasst von
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 Dongen
Publikationsdatum
01.11.2006
Verlag
Springer-Verlag
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 11/2006
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-006-0160-0

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