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Cure of Micrometastatic B-Cell Lymphoma in a SCID Mouse Model Using (213)Bi-Anti-CD20 Monoclonal Antibody

We studied the feasibility of using the α-emitting (213)Bi-anti-CD20 therapy with direct bioluminescent tracking of micrometastatic human B-cell lymphoma in a SCID mouse model. Methods: A highly lethal SCID mouse model of minimal-tumor-burden disseminated non-Hodgkin lymphoma (NHL) was established u...

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Autores principales: Havlena, Gregory T., Kapadia, Nirav S., Huang, Peng, Song, Hong, Engles, James, Brechbiel, Martin, Sgouros, George, Wahl, Richard L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society of Nuclear Medicine 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9841256/
https://www.ncbi.nlm.nih.gov/pubmed/35981897
http://dx.doi.org/10.2967/jnumed.122.263962
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author Havlena, Gregory T.
Kapadia, Nirav S.
Huang, Peng
Song, Hong
Engles, James
Brechbiel, Martin
Sgouros, George
Wahl, Richard L.
author_facet Havlena, Gregory T.
Kapadia, Nirav S.
Huang, Peng
Song, Hong
Engles, James
Brechbiel, Martin
Sgouros, George
Wahl, Richard L.
author_sort Havlena, Gregory T.
collection PubMed
description We studied the feasibility of using the α-emitting (213)Bi-anti-CD20 therapy with direct bioluminescent tracking of micrometastatic human B-cell lymphoma in a SCID mouse model. Methods: A highly lethal SCID mouse model of minimal-tumor-burden disseminated non-Hodgkin lymphoma (NHL) was established using human Raji lymphoma cells transfected to express the luciferase reporter. In vitro and in vivo radioimmunotherapy experiments were conducted. Single- and multiple-dose regimens were explored, and results with (213)Bi-rituximab were compared with various controls, including no treatment, free (213)Bi radiometal, unlabeled rituximab, and (213)Bi-labeled anti-HER2/neu (non–CD20-specific antibody). (213)Bi-rituximab was also compared in vivo with the low-energy β-emitter (131)I-tositumomab and the high-energy β-emitter (90)Y-rituximab. Results: In vitro studies showed dose-dependent target-specific killing of lymphoma cells with (213)Bi-rituximab. Multiple in vivo studies showed significant and specific tumor growth delays with (213)Bi-rituximab versus free (213)Bi, (213)Bi-labeled control antibody, or unlabeled rituximab. Redosing of (213)Bi-rituximab was more effective than single dosing. With a single dose of therapy given 4 d after intravenous tumor inoculation, disease in all untreated controls, and in all mice in the 925-kBq (90)Y-rituximab group, progressed. With 3,700 kBq of (213)Bi-rituximab, 75% of the mice survived and all but 1 survivor was cured. With 2,035 kBq of (131)I-tositumomab, 75% of the mice were tumor-free by bioluminescent imaging and 62.5% survived. Conclusion: Cure of micrometastatic NHL is achieved in most animals treated 4 d after intravenous tumor inoculation using either (213)Bi-rituximab or (131)I-tositumomab, in contrast to the lack of cures with unlabeled rituximab or (90)Y-rituximab or if there was a high tumor burden before radioimmunotherapy. α-emitter–labeled anti-CD20 antibodies are promising therapeutics for NHL, although a longer-lived α-emitter may be of greater efficacy.
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spelling pubmed-98412562023-04-19 Cure of Micrometastatic B-Cell Lymphoma in a SCID Mouse Model Using (213)Bi-Anti-CD20 Monoclonal Antibody Havlena, Gregory T. Kapadia, Nirav S. Huang, Peng Song, Hong Engles, James Brechbiel, Martin Sgouros, George Wahl, Richard L. J Nucl Med Basic Science Investigation We studied the feasibility of using the α-emitting (213)Bi-anti-CD20 therapy with direct bioluminescent tracking of micrometastatic human B-cell lymphoma in a SCID mouse model. Methods: A highly lethal SCID mouse model of minimal-tumor-burden disseminated non-Hodgkin lymphoma (NHL) was established using human Raji lymphoma cells transfected to express the luciferase reporter. In vitro and in vivo radioimmunotherapy experiments were conducted. Single- and multiple-dose regimens were explored, and results with (213)Bi-rituximab were compared with various controls, including no treatment, free (213)Bi radiometal, unlabeled rituximab, and (213)Bi-labeled anti-HER2/neu (non–CD20-specific antibody). (213)Bi-rituximab was also compared in vivo with the low-energy β-emitter (131)I-tositumomab and the high-energy β-emitter (90)Y-rituximab. Results: In vitro studies showed dose-dependent target-specific killing of lymphoma cells with (213)Bi-rituximab. Multiple in vivo studies showed significant and specific tumor growth delays with (213)Bi-rituximab versus free (213)Bi, (213)Bi-labeled control antibody, or unlabeled rituximab. Redosing of (213)Bi-rituximab was more effective than single dosing. With a single dose of therapy given 4 d after intravenous tumor inoculation, disease in all untreated controls, and in all mice in the 925-kBq (90)Y-rituximab group, progressed. With 3,700 kBq of (213)Bi-rituximab, 75% of the mice survived and all but 1 survivor was cured. With 2,035 kBq of (131)I-tositumomab, 75% of the mice were tumor-free by bioluminescent imaging and 62.5% survived. Conclusion: Cure of micrometastatic NHL is achieved in most animals treated 4 d after intravenous tumor inoculation using either (213)Bi-rituximab or (131)I-tositumomab, in contrast to the lack of cures with unlabeled rituximab or (90)Y-rituximab or if there was a high tumor burden before radioimmunotherapy. α-emitter–labeled anti-CD20 antibodies are promising therapeutics for NHL, although a longer-lived α-emitter may be of greater efficacy. Society of Nuclear Medicine 2023-01 /pmc/articles/PMC9841256/ /pubmed/35981897 http://dx.doi.org/10.2967/jnumed.122.263962 Text en © 2023 by the Society of Nuclear Medicine and Molecular Imaging. https://creativecommons.org/licenses/by/4.0/Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: https://creativecommons.org/licenses/by/4.0/. Details: http://jnm.snmjournals.org/site/misc/permission.xhtml.
spellingShingle Basic Science Investigation
Havlena, Gregory T.
Kapadia, Nirav S.
Huang, Peng
Song, Hong
Engles, James
Brechbiel, Martin
Sgouros, George
Wahl, Richard L.
Cure of Micrometastatic B-Cell Lymphoma in a SCID Mouse Model Using (213)Bi-Anti-CD20 Monoclonal Antibody
title Cure of Micrometastatic B-Cell Lymphoma in a SCID Mouse Model Using (213)Bi-Anti-CD20 Monoclonal Antibody
title_full Cure of Micrometastatic B-Cell Lymphoma in a SCID Mouse Model Using (213)Bi-Anti-CD20 Monoclonal Antibody
title_fullStr Cure of Micrometastatic B-Cell Lymphoma in a SCID Mouse Model Using (213)Bi-Anti-CD20 Monoclonal Antibody
title_full_unstemmed Cure of Micrometastatic B-Cell Lymphoma in a SCID Mouse Model Using (213)Bi-Anti-CD20 Monoclonal Antibody
title_short Cure of Micrometastatic B-Cell Lymphoma in a SCID Mouse Model Using (213)Bi-Anti-CD20 Monoclonal Antibody
title_sort cure of micrometastatic b-cell lymphoma in a scid mouse model using (213)bi-anti-cd20 monoclonal antibody
topic Basic Science Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9841256/
https://www.ncbi.nlm.nih.gov/pubmed/35981897
http://dx.doi.org/10.2967/jnumed.122.263962
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