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dc.date.accessioned2021-01-28T20:54:26Z
dc.date.available2021-01-28T20:54:26Z
dc.date.created2020-11-04T15:06:20Z
dc.date.issued2020
dc.identifier.citationMalenge, Marion Masitsa Patzke, Sebastian Ree, Anne Hansen Stokke, Trond Ceuppens, Peter Middleton, Brian Dahle, Jostein Repetto-Llamazares, Ada H.V. . 177Lu-lilotomab satetraxetan has the potential to counteract resistance to rituximab in non-Hodgkin lymphoma. Journal of Nuclear Medicine. 2020, 61(10), 1468-1475
dc.identifier.urihttp://hdl.handle.net/10852/82704
dc.description.abstractPatients with non-Hodgkin lymphoma (NHL) who are treated with rituximab may develop resistant disease, often associated with changes in expression of CD20. The next-generation β-particle–emitting radioimmunoconjugate 177Lu-lilotomab-satetraxetan (Betalutin) was shown to up-regulate CD20 expression in different rituximab-sensitive NHL cell lines and to act synergistically with rituximab in a rituximab-sensitive NHL animal model. We hypothesized that 177Lu-lilotomab-satetraxetan may be used to reverse rituximab resistance in NHL. Methods: The rituximab-resistant Raji2R and the parental Raji cell lines were used. CD20 expression was measured by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) was measured by a bioluminescence reporter assay. The efficacies of combined treatments with 177Lu-lilotomab-satetraxetan (150 or 350 MBq/kg) and rituximab (4 × 10 mg/kg) were compared with those of single agents or phosphate-buffered saline in a Raji2R-xenograft model. Cox regression and the Bliss independence model were used to assess synergism. Results: Rituximab binding in Raji2R cells was 36% ± 5% of that in the rituximab-sensitive Raji cells. 177Lu-lilotomab-satetraxetan treatment of Raji2R cells increased the binding to 53% ± 3% of the parental cell line. Rituximab ADCC induction in Raji2R cells was 20% ± 2% of that induced in Raji cells, whereas treatment with 177Lu-lilotomab-satetraxetan increased the ADCC induction to 30% ± 3% of that in Raji cells, representing a 50% increase (P < 0.05). The combination of rituximab with 350 MBq/kg 177Lu-lilotomab-satetraxetan synergistically suppressed Raji2R tumor growth in athymic Foxn1nu mice. Conclusion: 177Lu-lilotomab-satetraxetan has the potential to reverse rituximab resistance; it can increase rituximab binding and ADCC activity in vitro and can synergistically improve antitumor efficacy in vivo.
dc.languageEN
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.title177Lu-lilotomab satetraxetan has the potential to counteract resistance to rituximab in non-Hodgkin lymphoma
dc.typeJournal article
dc.creator.authorMalenge, Marion Masitsa
dc.creator.authorPatzke, Sebastian
dc.creator.authorRee, Anne Hansen
dc.creator.authorStokke, Trond
dc.creator.authorCeuppens, Peter
dc.creator.authorMiddleton, Brian
dc.creator.authorDahle, Jostein
dc.creator.authorRepetto-Llamazares, Ada H.V.
cristin.unitcode185,53,49,0
cristin.unitnameKreftklinikken
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.cristin1844958
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal of Nuclear Medicine&rft.volume=61&rft.spage=1468&rft.date=2020
dc.identifier.jtitleJournal of Nuclear Medicine
dc.identifier.volume61
dc.identifier.issue10
dc.identifier.startpage1468
dc.identifier.endpage1475
dc.identifier.doihttps://doi.org/10.2967/jnumed.119.237230
dc.identifier.urnURN:NBN:no-85535
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.source.issn0161-5505
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/82704/4/1468.full.pdf
dc.type.versionPublishedVersion


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