title: Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model.
abstract: α-Emitting radionuclides deposit a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD). To evaluate this hypothesis, (211)At-labeled 1F5 monoclonal antibody (mAb) (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to (211)At-labeled 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor-bearing animals treated with doses of up to 48 µCi of (211)At-labeled anti-CD20 mAb ([(211)At]1F5-B10) experienced modest responses (0% cures but two- to threefold prolongation of survival compared with negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with (211)At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity was observed in the cured animals receiving 15 µCi of [(211)At]1F5-B10. These findings suggest that α-emitters are highly efficacious in MRD settings, where isolated cells and small tumor clusters prevail.
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Medicine and.
authors: Damian J
authors: http://orcid.org/0000-0003-0477-1446
authors: DJ
authors: Green
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Medicine and.
authors: Mazyar
authors: http://orcid.org/0000-0002-3365-6562
authors: M
authors: Shadman
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
authors: Jon C
authors: JC
authors: Jones
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
authors: Shani L
authors: SL
authors: Frayo
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
authors: Aimee L
authors: AL
authors: Kenoyer
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
authors: Mark D
authors: http://orcid.org/0000-0002-5968-9872
authors: MD
authors: Hylarides
authors: Radiation Oncology, University of Washington, Seattle, WA;
authors: Donald K
authors: DK
authors: Hamlin
authors: Radiation Oncology, University of Washington, Seattle, WA;
authors: D Scott
authors: DS
authors: Wilbur
authors: Radiation Oncology, University of Washington, Seattle, WA;
authors: Ethan R
authors: http://orcid.org/0000-0002-9091-1515
authors: ER
authors: Balkan
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
authors: Yukang
authors: http://orcid.org/0000-0001-8586-8682
authors: Y
authors: Lin
authors: Pacific Northwest National Laboratory, Richland, WA; and.
authors: Brian W
authors: http://orcid.org/0000-0002-3435-8268
authors: BW
authors: Miller
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
authors: Sofia H L
authors: http://orcid.org/0000-0001-7656-349X
authors: SH
authors: Frost
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Medicine and.
authors: Ajay K
authors: AK
authors: Gopal
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Medicine and.
authors: Johnnie J
authors: http://orcid.org/0000-0002-1361-4680
authors: JJ
authors: Orozco
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
authors: Theodore A
authors: http://orcid.org/0000-0002-8182-3652
authors: TA
authors: Gooley
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
authors: Kelly L
authors: KL
authors: Laird
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Medicine and.
authors: Brian G
authors: http://orcid.org/0000-0002-4718-8288
authors: BG
authors: Till
authors: Department of Radiation Physics, University of Gothenberg, Gothenberg, Sweden.
authors: Tom
authors: http://orcid.org/0000-0002-3375-9473
authors: T
authors: Bäck
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Medicine and.
authors: Brenda M
authors: http://orcid.org/0000-0002-9767-9739
authors: BM
authors: Sandmaier
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Medicine and.
authors: John M
authors: http://orcid.org/0000-0001-5745-8125
authors: JM
authors: Pagel
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Departments of Medicine and.
authors: Oliver W
authors: http://orcid.org/0000-0002-3147-8037
authors: OW
authors: Press
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology*; D001246:Astatine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D019169:Jurkat Cells; D016393:Lymphoma, B-Cell / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D016499:Radioimmunotherapy; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D018796:Immunoconjugates; D001246:Astatine
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