title: In vitro testing of the leukaemia monoclonal antibody WM-53 labeled with alpha and beta emitting radioisotopes.
abstract: We report the preparation and testing of a new alpha emitting radio-immunoconjugate (RIC) against acute myeloid leukaemia (AML) using CD33 positive monoclonal antibody WM-53 (specific for HL-60 cell line). Using cyclic anhydride of diethylenetriaminepentacetic acid (cDTPAa) as chelator, antibody was labeled with 213Bi (alpha), 149Tb (alpha), 153Sm (beta) and 152Tb (positron). In vitro testing showed high labeling efficiency (90-95%) and stability (11-19% leaching) with immunoreactivity virtually the same before and after labeling. DNA synthesis data and MTS cell survival were compared for all RICs. Only the alpha emitter was found to be capable of inhibiting DNA synthesis and had selective cell kill with activity as low as 2-3 microCi. The high stability and outstanding cytotoxicity of the 213Bi conjugate provides the basis for targeted alpha therapy for the control of metastatic and disseminated cancer such as AML.
authors.affiliation: Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, NSW 2217, Kogarah, Australia.
authors.forename: Syed M
authors.initials: SM
authors.lastname: Abbas Rizvi
authors.forename: A J
authors.initials: AJ
authors.lastname: Henniker
authors.forename: G
authors.initials: G
authors.lastname: Goozee
authors.forename: B J
authors.initials: BJ
authors.lastname: Allen
mesh_terms: D000208:Acute Disease; D000512:Alpha Particles / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D001610:Beta Particles / Q000627:therapeutic use; D002470:Cell Survival / Q000528:radiation effects; D002614:Chelating Agents / Q000737:chemistry; D004261:DNA Replication / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000528:radiation effects; D005434:Flow Cytometry; D018922:HL-60 Cells / Q000528:radiation effects; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007553:Isotope Labeling; D007951:Leukemia, Myeloid / Q000235:genetics / Q000532:radiotherapy*; D004369:Pentetic Acid / Q000737:chemistry; D063268:Sialic Acid Binding Ig-like Lectin 3
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D002614:Chelating Agents; D004273:DNA, Neoplasm; D018796:Immunoconjugates; D063268:Sialic Acid Binding Ig-like Lectin 3; D004369:Pentetic Acid