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Nuklearmedizin 2005; 44(04): 166-177
DOI: 10.1055/s-0038-1625104
Original Articles
Schattauer GmbH

Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan

Clinical considerations, radiopharmacy, radiation protection, perspectivesRadioimmuntherapie mit 90Y-markiertem Ibritumomab-TiuxetanKlinik, Radiopharmazie, Strahlenschutz, Perspektiven
K. Schomäcker
1   Klinik und Poliklinik für Nuklearmedizin
,
M. Dietlein
1   Klinik und Poliklinik für Nuklearmedizin
,
R. Schnell
2   Klinik I für Innere Medizin der Universität zu Köln
,
J. Pinkert
3   Schering Deutschland GmbH, Berlin
,
W. Eschner
1   Klinik und Poliklinik für Nuklearmedizin
,
B. Zimmermanns
1   Klinik und Poliklinik für Nuklearmedizin
,
T. Fischer
1   Klinik und Poliklinik für Nuklearmedizin
,
A. Engert
2   Klinik I für Innere Medizin der Universität zu Köln
,
H. Schicha
1   Klinik und Poliklinik für Nuklearmedizin
› Author Affiliations
Further Information

Publication History

Eingegangen: 27 December 2004

angenommen nach Revision: 03 February 2005

Publication Date:
11 January 2018 (online)

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Summary

90Y-ibritumomab tiuxetan (Zevalin®) is currently approved for radioimmunotherapy of patients with relapsed or refractory follicular non-Hodgkin’s lymphoma pretreated with rituximab. Future directions are the combined use of 90Y-ibritumomab tiuxetan as part of the initial treatment and as first-line multi-agent therapy of relapsed disease. Current studies investigate patients with other than follicular indolent histologies, e. g. diffuse large cell lymphoma. Labelling of 90Y ibritumomab tiuxetan is a safe procedure, the radiochemical purity is not disturbed by a higher room temperature or by metallic impurity. Quality control is recommended by thin layer chromatography (TLC), strips >15 cm are favourable. TLC cannot distinguish between the correctly radiolabelled antibodies and radiocolloid impurity. If necessary, additional HPLC should be performed. Radiocolloid impurities are absorbed to the solid phase and do not reach the eluate. If the radiochemical purity test is insufficient (<95%), the additional cleaning using EconoPac 10 DG columns (Biorad, Hercules, CA, USA) is a reliable procedure to reduce the percentage of free radionuclide. However, this procedure is not part of the approval.

Zusammenfassung

Die Radioimmuntherapie mit 90Y-Ibritumomab-Tiuxetan (Zevalin®) ist bei Patienten mit einem rezidivierten oder refraktären follikulären Lymphom, die mit Rituximab vorbehandelt sind, zugelassen. Die aktuellen Studien über einen konsolidierenden Einsatz von 90Y-Ibritumomab-Tiuxetan nach Chemotherapie in der Primärbehandlung und im ersten Rezidiv scheinen erfolgversprechende neue Therapieansätze darzustellen. Für eine Verbreiterung des Indikationsspektrums auf das diffus großzellige Lymphom existieren erste günstige Studienergebnisse. Dabei erweist sich die Markierung von 90Y-Ibritumomab-Tiuxetan als eine relativ belastbare radiochemische Markierungsprozedur, die auch in gewissem Umfang störende Parameter wie höhere Temperatur oder erhöhte Schwermetallkonzentration toleriert. Für die Qualitätskontrolle mittels Dünnschichtchromatographie (TLC) werden Streifen >15 cm empfohlen. Prinzipiell kann die TLC nicht zwischen Radiokolloiden und markierten Proteinen unterscheiden. Im Zweifelsfall sollte zusätzlich eine HPLC durchgeführt werden: Kolloide verbleiben auf der Säule und erscheinen nicht im Eluat. Im Falle einer Fehlmarkierung ist die Chromatographie mit Econo- Pac-10DG-Entsalzungssäulen (Biorad, Hercules, CA, USA) eine zuverlässige Möglichkeit, das kostenintensive Radiopharmakon noch zu retten. Allerdings ist diese Methode nicht Bestandteil der Zulassung.

Keywords

Ibritumomab tiuxetan - Zevalin® - yttrium-90 - radioimmunotherapy - activimeter - radiation protection

Schlüsselwörter

Ibritumomab-Tiuxetan - Zevalin® - Yttrium-90 - Radioimmuntherapie - Aktivimeter - Strahlenschutz
 

  • Literatur

  • 1 Ansell SM, Ristow KM, Habermann TM. et al. Subsequent chemotherapy regimes are well tolerated after radioimmunotherapy with yttrium-90 ibritumomab tiuxetan for non-Hodgkin’s lymphoma. J Clin Oncol 2002; 20: 3885-90.
    CrossrefPubMedSearch in Google Scholar
  • 2 Bartlett NL, Witzig T, Gordon L. et al. 90Y-ibritumomab tiuxetan (Zevalin) radioimmunotherapy for transformed B-cell non-Hodgkin’s lymphoma (NHL) patients. Proc Am Soc Clin Oncol 2002; 21: 14.
    Search in Google Scholar
  • 3 Behr TM. Quo vadis Radioimmun- und Radiopeptidtherapie? Welche Rolle spielen Sie künftig im klinischen Alltag?. Nuklearmedizin 2002; 41: 230-2.
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Behr TM, Gotthardt M, Becker W. et al. Radioiodination of monoclonal antibodies, proteins and peptides for diagnosis and therapy: a review of standardized, reliable and safe procedures for clinical grade levels kBq to GBq in the Göttingen/ Marburg experience. Nuklearmedizin 2002; 41: 71-9.
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Borghaei H, Schilder RJ. Safety and efficacy of radioimmunotherapy with yttrium 90 ibritumomab tiuxetan (Zevalin). Sem Nucl Med 2004; 34 (Suppl. 01) 4-9.
    Search in Google Scholar
  • 6 Cheson BD. Radioimmunotherapy with yttrium- 90 ibritumomab tiuxetan: future directions. In: Cheson BD, Leonard JP, Raubitschek A. et al. (Hrsg) Ibritumomab tiuxetan (Zevalin) in non- Hodgkin’s lymphoma. The Oncology Group; 2003
    Search in Google Scholar
  • 7 Chinn PC, Leonard JE, Rosenberg J. et al. Preclinical evaluation of 90Y-labeled anti-CD20 monoclonal antibody for treatment of non-Hodgkin’s lymphoma. International J Oncol 1999; 15: 1017-25.
    Search in Google Scholar
  • 8 Conti PS. Radioimmuntherapy with yttrium-90 ibritumomab tiuxetan (Zevalin) : the role of the nuclear medicine physician. Sem Nucl Med 2004; 43 (Suppl. 01) 2-3.
    Search in Google Scholar
  • 9 Conti PS, White C, Pieslor P. et al. Incidence of altered biodistribution detected by indium 111 (111In) imaging prior to yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin®) radioimmunotherapy: results from a Zevalin imaging registry. Blood 2004; 104: 4570.
    Search in Google Scholar
  • 10 Czuczman M, Witzig TE, Gaston I. et al. Zevalin radioimmunotherapy is not associated with an increased incidence of secondary myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Blood 2002; 100: 357a.
    Search in Google Scholar
  • 11 Emmanouilides C, Murray JL, Vo K. et al. Earlier treatment with Yttrium-90 ibritumomab tiuxetan (Zevalin®) radioimmuntherapy is associated with higher response rates and longer durations of response in patients with previously treated B-cell non-Hodgkin’s lymphoma (NHL): results with second- line therapy. Blood 2003; 102: 4949.
    Search in Google Scholar
  • 12 Fischer M, Behr T, Grünwald F. et al. Leitlinie für die Radioimmuntherapie des rezidivierenden oder refraktären CD20-positiven follikulären B-Zell-Non-Hodgkin-Lymphoms. Nuklearmedizin 2004; 43: 171-6.
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Flinn IW, Kahl BS, Frey E. et al. Dose finding trial of yttrium 90 (90Y) ibritumomab tiuxetan with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory B-cell non- Hodgkin’s lymphoma. Blood 2004; 104: 897.
    Search in Google Scholar
  • 14 Gas-, Elektrizitäts- und Wasserwerk Köln www.gewkoelnag.de
  • 15 Ghielmini M, Schmitz S-FH, Cogliatti S. et al. Prolonged treatment with rituximab significantly improves event free survival and duration of response in patients with follicular lymphoma: a randomised SAKK trial. Blood 2002; 100: 161a.
    Search in Google Scholar
  • 16 Gordon LI, Molina A, Witzig T. et al. Durable responses after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: longterm follow-up of a phase 1/ 2 study. Blood 2004; 103: 4429-31.
    CrossrefPubMedSearch in Google Scholar
  • 17 Gordon LI, Witzig T, Emmanouilides C. et al. 90Y ibritumomab (Zevalin) in aggressive non- Hodgkin’s lymphoma : analysis of response and toxicity. ProcAm Soc Clin Oncol 2002; 21: 266a.
    Search in Google Scholar
  • 18 Gordon LI, Witzig T, Molina A. et al. Yttrium 90-labeled ibritumomab tiuxetan radioimmunotherapy produces high response rates and durable remissions in patients with previously treated B-cell lymphoma. Clin Lymphoma 2004; 5: 98-101.
    PubMedSearch in Google Scholar
  • 19 Hainsworth JD, Litchy S, Barton JH. et al. Singleagent rituximab as first-line and maintenance treatment for patients with chronic lymphatic leukaemia or small lymphocytic lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2003; 21: 1746-51.
    CrossrefPubMedSearch in Google Scholar
  • 20 Horning SJ. Future directions in radioimmunotherapy for B-cell lymphoma. Semin Oncol 2003; 30 (Suppl. 17) 29-34.
    PubMedSearch in Google Scholar
  • 21 Jacobs SA, McCook B, Torok F. et al. Evaluation of yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin®) in patients with non-Hodgkin’s lymphoma (NHL) having previously received autologous stem cell transplant (ASCT). Blood 2004; 104: 5238.
    Search in Google Scholar
  • 22 Kaminski MS, Tuck M, Regan D. et al. High response rate and durable remissions in patients with previously untreated, advanced-stage, follicular lymphoma treated with tositumomab and iodine- 131 tositumomab (Bexxar). Blood 2002; 11: 356a.
    Search in Google Scholar
  • 23 Knox S, Goris M, Trisler K. et al. Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma. Clin Cancer Res 1999; 2: 457-70.
    Search in Google Scholar
  • 24 Morschhauser F, Huglo D, Martinelli G. et al. Yttrium- 90 ibritumomab tiuxetan (Zevalin) for patients with relapsed/refractory diffuse large B-cell lymphoma not appropriate for autologous stem cell transplantation: results of an open-label phase II trial. Blood 2004; 104: 130.
    Search in Google Scholar
  • 25 Nademanee A, Molina A, Forman SJ. et al. A phase I/II trial of high-dose radioimmunotherapy (RIT) with Zevalin in combination with high-dose etoposide (VP-16) and cyclophosphamide (CY) followed by autologous stem cell transplant (ASCT) in patients with poor-risk or relapsed B-cell non-Hodgkin’s lymphoma (NHL). Blood 2002; 100 182a 679.
    Search in Google Scholar
  • 26 Noßke D. Retentions- und Ausscheidungsdaten sowie Dosiskoeffizienten für die Inkorporationsüberwachung. BfS-SG-02/03, , Salzgitter: Bundesamt für Strahlenschutz; 2003
    Search in Google Scholar
  • 27 Oki Y, Pro B, Delpassand E. et al. A phase II study of yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin ®) for treatment of patients with relapsed and refractory mantle cell lymphoma (MCL). Blood 2004; 104: 2632.
    Search in Google Scholar
  • 28 Rödel R, Ebert A, Reichmann K. et al. Effizienz von Spritzenabschirmungen bei Radionuklidanwendung zur Radiosynoviorthese. Nuklearmedizin 2003; 42: 50-3.
    Thieme ConnectPubMedSearch in Google Scholar
  • 29 Roeder N. Anpassungsbedarf der Vergütung von Krankenhausleistungen für 2005. Gutachten im Auftrag der Deutschen Krankenhausgesellschaft. Münster: 2004 www.uni-muenster.de/index.html
    PubMedSearch in Google Scholar
  • 30 Schilder RJ, Witzig T, Gordon L. et al. 90Y ibritumomab tiuxetan (Zevalin) radioimmuntherapy does not preclude effective delivery of subsequent therapy for lymphoma. Proc Am Soc Clin Oncol 2002; 21: 267a (1064).
    Search in Google Scholar
  • 31 Schilder RJ, Witzig TE, Flinn I. et al. Yttrium 90 ibritumomab tiuxetan (Zevalin®) induces longterm responses in patients with relapsed or refractory follicular lymphoma (FL). Blood 2004; 104: 2629.
    Search in Google Scholar
  • 32 Siegel JA, Zimmerman BE, Kodimer K. et al. Accurate dose calibrator activity measurement of 90Yibritumomab tiuxetan. J Nucl Med 2004; 45: 450-4.
    PubMedSearch in Google Scholar
  • 33 Spies SM. Imaging and dosing in radioimmunotherapy with yttrium 90 ibritumomab tiuxetan (Zevalin). Sem Nucl Med 2004; 34 (Suppl. 01) 10-3.
    Search in Google Scholar
  • 34 Staak JO, Dietlein M, Engert A. et al. Nuklearmedizinische Aspekte in der Diagnostik und Therapie des Hodgkin-Lymphoms. Nuklearmedizin 2003; 42: 19-24.
    Thieme ConnectPubMedSearch in Google Scholar
  • 35 Strahlenschutz in der Medizin. Richtlinie nach der Verordnung über den Schutz vor Schäden durch ionisierende Strahlen (Strahlenschutzverordnung). Bundesanzeiger 207a vom 7.11.2002.
  • 36 Strahlenschutzkommission. Strahlenschutz bei der Therapie mit β-Strahlern in flüssiger Form im Rahmen einer Brachytherapie, Radiosynoviorthese der Strahlenschutzkommission am 31.3./1.4. 2003.
  • 37 Sweetenham JW, Dicke K, Arcaroli J. et al. Efficacy and safety of yttrium 90 ibritumomab tiuxetan (Zevalin®) therapy with rituximab maintenance in patients with untreated low-grade follicular lymphoma. Blood 2004; 104: 2633.
    Search in Google Scholar
  • 38 Wagner Jr HN, Wiseman GA, Marcus CS. et al. Administration guidelines for radioimmunotherapy of non-Hodgkin’s lymphoma with 90Y-labeled anti-CD20 monoclonal antibody. J Nucl Med 2002; 43: 267-72.
    PubMedSearch in Google Scholar
  • 39 Winter JN, Inwards DJ, Spies S. et al. 90Y ibritumomab tiuxetan (Zevalin®, 90YZ) doses higher than .4 mCi/kg may be safely combined with high-dose BEAM and autotransplant: the role for dosimetry. Blood 2004; 104: 1162.
    Search in Google Scholar
  • 40 Wiseman G, Leigh B, Witzig T. et al. Radiation exposure is very low to the family members of patients treated with yttrium-90 Zevalin anti-CD20 monoclonal antibody therapy for lymphoma. Eur J Nucl Med 28: 1198 2001;
    Search in Google Scholar
  • 41 Wiseman GA, Leigh BR, Erwin W. Urinary clearance of 90Y activity following Zevalin radioimmunotherapy of B-cell non-Hodgkin’s lymphoma. J Nucl Med 2001; 42: 268P.
    Search in Google Scholar
  • 42 Wiseman GA, Gordon LI, Multani PS. et al. Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood 2002; 99: 4336-42.
    CrossrefPubMedSearch in Google Scholar
  • 43 Wiseman GA, Kornmehl E, Leigh B. et al. Radiation dosimetry results and safety correlations from 90Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin`s lymphoma: combined data from 4 clinical trials. J Nucl Med 2003; 44: 465-74.
    PubMedSearch in Google Scholar
  • 44 Wiseman GA, Colgan JP, Micallef IN. et al. Interim safety results of a phase I trial of two sequential doses of yttrium-90 ibritumomab tiuxetan for previously treated patients with low-grade non- Hodgkin’s lymphoma (NHL). Proc Am Soc Clin Oncol 2003; 22: 575 (2312).
    Search in Google Scholar
  • 45 Wiseman G, Conti P, Vo K. et al. Evaluation of baseline body-weight dosing of 90Y ibritumomab tiuxetan (Zevalin®) radioimmunotherapy in patients with relapsed or refractory B-cell non- Hodgkin’s lymphoma. Blood 2004; 104: 2634.
    Search in Google Scholar
  • 46 Witzig TE, Gordon LI, Cabanillas F. 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: 2453-63.
    CrossrefPubMedSearch in Google Scholar
  • 47 Witzig TE, Flinn IW, Gordon LI. et al. Treatment with ibritumomab tiuxetan radioimmuntherapy in patients with rituximab-refractory follicular non- Hodgkin’s lymphoma. J Clin Oncol 2002; 20: 3262-9.
    CrossrefPubMedSearch in Google Scholar
  • 48 Witzig TE, White CA, Gordon LI. et al. Safety of yttrium-90 ibritumomab tiuxetan radioimmuntherapy for relapsed low-grade, follicular, or transformed non-Hodgkin’s lymphoma. J Clin Oncol 2003; 21: 1263-70.
    CrossrefPubMedSearch in Google Scholar
  • 49 Witzig TE, White CA, Wiseman GA. et al. Phase I/II Trial of IDEC-Y2B8 Radioimmunotherapy for treatment of relapsed or refractory CD 20+ B-cell non-Hodgkin’s lymphoma. J Clin Oncol 1999; 17: 3793-803.
    CrossrefPubMedSearch in Google Scholar
  • 50 Zanzonico PB, Binkert BL, Goldsmith SJ. Bremsstrahlung radiation exposure from pure β-ray emitters. J Nucl Med 1999; 40: 1024-8.
    PubMedSearch in Google Scholar
  • 51 Zimmer AM. Logistics of radioimmunotherapy with yttrium 90 ibritumomab tiuxetan (Zevalin). Sem Nucl Med 2004; 34 (Suppl. 01) 14-9.
    Search in Google Scholar
  • 52 Zimmer AM, Carey AM, Spies SM. Effectiveness of specific vial shields in reducing radiation exposure fromY-90 Zevalin. J Nucl Med 2002; 43: 45P.
    Search in Google Scholar
  • 53 Zhu X. Radiation safety considerations with yttrium 90 ibritumomab tiuxetan (Zevalin). Sem Nucl Med 2004; 34 (Suppl. 01) 20-3.
    Search in Google Scholar
  • 54 Strahlenschutzkommission. Radioimmuntherapie mit 90Y-Ibritumomab-Tiuxetan (90Y-Zevalin). Empfehlung der Strahlenschutzkommission, verabschiedet in der 198. Sitzung der SSK am 17.2.2005.