Demonstration of highly specific toxicity of the α-emitting radioimmunoconjugate 211At-rituximab against non-Hodgkin"s lymphoma cells

被引:38
作者
Aurlien, E
Larsen, RH
Kvalheim, G
Bruland, OS
机构
[1] Norwegian Radium Hosp, Dept Oncol, N-0310 Oslo, Norway
[2] Univ Oslo, Dept Chem, Sect D, N-0315 Oslo, Norway
[3] Norwegian Radium Hosp, Clin Stem Cell Labs, N-0310 Oslo, Norway
关键词
clonogenic survival; lymphoma cells; bone marrow; alpha-emitter; radioimmunoconjugate; rituximab;
D O I
10.1054/bjoc.2000.1453
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 At-211-rituximab (Rituxan(R) or MabThera(TM)) and plated in clonogenic assays for survival analyses. Following 1 h incubation with At-211-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 At-211-rituximab in Balb/c mice showed similar stability as that of the iodinated analogue. The data indicate that testing of At-211-rituximab in human patients is warranted. (C) 2000 Cancer Research Campaign.
引用
收藏
页码:1375 / 1379
页数:5
相关论文
共 25 条
[1]  
ARMITAGE JO, 1993, NEW ENGL J MED, V328, P1023
[2]   EFFECT OF OXYGEN ON IMPAIRMENT OF PROLIFERATIVE CAPACITY OF HUMAN CELLS IN CULTURE BY IONIZING RADIATIONS OF DIFFERENT LET [J].
BARENDSE.GW ;
KOOT, CJ ;
VANKERSE.GR ;
BEWLEY, DK ;
FIELD, SB ;
PARNELL, CJ .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY AND RELATED STUDIES IN PHYSICS CHEMISTRY AND MEDICINE, 1966, 10 (04) :317-&
[3]  
Behr TM, 1999, CANCER RES, V59, P2635
[4]   ASTATINE-211 - ITS POSSIBLE APPLICATIONS IN CANCER-THERAPY [J].
BROWN, I .
APPLIED RADIATION AND ISOTOPES, 1986, 37 (08) :789-&
[5]   Cancer therapy with radiolabeled antibodies - An overview [J].
Bruland, OS .
ACTA ONCOLOGICA, 1995, 34 (08) :1085-1094
[6]   INVITRO COLONY ASSAY FOR HUMAN TUMORS GROWN IN IMMUNE-SUPPRESSED MICE AND TREATED INVIVO WITH CYTOTOXIC AGENTS [J].
COURTENAY, VD ;
MILLS, J .
BRITISH JOURNAL OF CANCER, 1978, 37 (02) :261-268
[7]  
DYER MJS, 1990, BLOOD, V75, P709
[8]  
Eaves CJ, 1991, J TISSUE CULTURE MET, V13, P55
[9]  
Hall EJ, 1994, RADIOBIOLOGY RADIOLO, V1994, P153
[10]  
Harrison A, 1987, NCI Monogr, P157