title: Validation of 213Bi-alpha radioimmunotherapy for multiple myeloma.
abstract: 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%).
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U463, Institut de Biologie, Nantes, France.
authors.forename: O
authors.initials: O
authors.lastname: Couturier
authors.forename: A
authors.initials: A
authors.lastname: Faivre-Chauvet
authors.forename: I V
authors.initials: IV
authors.lastname: Filippovich
authors.forename: P
authors.initials: P
authors.lastname: Thédrez
authors.forename: C
authors.initials: C
authors.lastname: Saï-Maurel
authors.forename: M
authors.initials: M
authors.lastname: Bardiès
authors.forename: A K
authors.initials: AK
authors.lastname: Mishra
authors.forename: M
authors.initials: M
authors.lastname: Gauvrit
authors.forename: G
authors.initials: G
authors.lastname: Blain
authors.forename: C
authors.initials: C
authors.lastname: Apostolidis
authors.forename: R
authors.initials: R
authors.lastname: Molinet
authors.forename: J C
authors.initials: JC
authors.lastname: Abbe
authors.forename: R
authors.initials: R
authors.lastname: Bataille
authors.forename: J
authors.initials: J
authors.lastname: Wijdenes
authors.forename: J F
authors.initials: JF
authors.lastname: Chatal
authors.forename: M
authors.initials: M
authors.lastname: Chérel
mesh_terms: 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
chemical_list: D001729:Bismuth; D013936:Thymidine