Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan

 

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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.

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