title: Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab.
abstract: This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an intravenous graft of 5.10(6) Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300 micro g unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%+/-4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%+/-2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with (149)Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach.
authors.affiliation: Division of Nuclear Medicine, University Hospital of Geneva, 24 Rue Micheli du Crest, 1211 Geneva 14, Switzerland. gerd.beyer@hcuge.ch
authors.forename: G-J
authors.initials: GJ
authors.lastname: Beyer
authors.forename: M
authors.initials: M
authors.lastname: Miederer
authors.forename: S
authors.initials: S
authors.lastname: Vranjes-Durić
authors.forename: J J
authors.initials: JJ
authors.lastname: Comor
authors.forename: G
authors.initials: G
authors.lastname: Künzi
authors.forename: O
authors.initials: O
authors.lastname: Hartley
authors.forename: R
authors.initials: R
authors.lastname: Senekowitsch-Schmidtke
authors.forename: D
authors.initials: D
authors.lastname: Soloviev
authors.forename: F
authors.initials: F
authors.lastname: Buchegger
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D019317:Evidence-Based Medicine / Q000379:methods; D005260:Female; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy*; D051379:Mice; D016513:Mice, SCID; D009928:Organ Specificity; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D015203:Reproducibility of Results; D000069283:Rituximab; D013534:Survival; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; C494619:terbium-rituximab; D000069283:Rituximab