Demonstration of highly specific toxicity of the alpha-emitting radioimmunoconjugate(211)At-rituximab against non-Hodgkin's lymphoma cells.
The ability of an alpha-emitter conjugated to a chimaeric anti-CD20 monoclonal antibody to kill selectively human B-lymphoma cells in vitro is reported. Two B-lymphoma cell lines RAEL and K422, and normal haematopoietic progenitor cells from human bone marrow aspirates were incubated with(211)At-rituximab (Rituxan(R) or MabTheratrade mark) and plated in clonogenic assays for survival analyses. Following 1 h incubation with(211)At-rituximab, in concentrations which gave an initial activity of 50 kBq ml(-1), a high tumour cell to normal bone marrow cell toxicity ratio was obtained; 4.1 to 1.0 log cell kill. Biodistribution studies of(211)At-rituximab in Balb/c mice showed similar stability as that of the iodinated analogue. The data indicate that testing of(211)At-rituximab in human patients is warranted.
Aurlien
E
E
Department of Oncology, The Norwegian Radium Hospital, Montebello, Oslo, N-0310, USA.
Larsen
R H
RH
Kvalheim
G
G
Bruland
O S
OS
D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001246:Astatine / Q000627:therapeutic use; D016923:Cell Death; D002470:Cell Survival; D006412:Hematopoietic Stem Cells / Q000528:radiation effects; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects*; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000532:radiotherapy*; D011868:Radioisotopes / Q000627:therapeutic use; D000069283:Rituximab; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D011868:Radioisotopes; D000069283:Rituximab; D001246:Astatine