Validation of 213Bi-alpha radioimmunotherapy for multiple myeloma.
The efficacy of radioimmunotherapy (RIT) with beta emitters has been clinically demonstrated in the treatment of refractory forms of lymphoma. Alpha-emitting radionuclides with a short half-life are also good potential candidates for RIT directed at tumor targets easily accessible to radioimmunoconjugate molecules and small enough to benefit from the short range of alpha particles (<100 microm). The purpose of this study was to demonstrate the feasibility of ex vivo purging of multiple myeloma-invaded bone marrow. Tumor cells were targeted by a specific monoclonal antibody (B-B4) coupled to 213Bi by a chelating agent (pentaacetic triamine diethylene p-aminobenzyl acid). The efficacy of alpha-RIT was assessed in vitro by analysis of thymidine incorporation, cell mortality, apoptosis of myeloma cells, and the study of nonspecific irradiation of hematopoietic cell lines not recognized by B-B4-pentaacetic triamine diethylene p-aminobenzyl acid immunoconjugate. High dose-dependent cell mortality of myeloma cells was found with radiolabeled B-B4, and this mortality was total at 30 kBq/10(5) cells. Cells were found in apoptotic state at rates of up to 40% for a dose of 7.4 kBq/10(5) cells. Nonspecific mortality was low compared with specific mortality (up to 1%).
Couturier
O
O
Institut National de la Santé et de la Recherche Médicale U463, Institut de Biologie, Nantes, France.
Faivre-Chauvet
A
A
Filippovich
I V
IV
Thédrez
P
P
Saï-Maurel
C
C
Bardiès
M
M
Mishra
A K
AK
Gauvrit
M
M
Blain
G
G
Apostolidis
C
C
Molinet
R
R
Abbe
J C
JC
Bataille
R
R
Wijdenes
J
J
Chatal
J F
JF
Chérel
M
M
D000512:Alpha Particles; D017209:Apoptosis / Q000528:radiation effects; D001729:Bismuth / Q000627:therapeutic use*; D002470:Cell Survival / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000528:radiation effects; D006801:Humans; D007553:Isotope Labeling; D009101:Multiple Myeloma / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001729:Bismuth; D013936:Thymidine