Affiliation: | (1) Division of Nuclear Medicine, University Hospital of Geneva, 24 Rue Micheli du Crest, 1211 Geneva 14, Switzerland;(2) Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, USA;(3) Laboratory of Radioisotopes, Vina Institute of Nuclear Sciences, Belgrade, Serbia and Montenegro;(4) Laboratory of Physics, Vina Institute of Nuclear Sciences, Belgrade, Serbia and Montenegro;(5) Department of Medical Biochemistry, University Medical Center, Geneva, Switzerland;(6) Clinic of Nuclear Medicine, Technical University of Munich, Munich, Germany;(7) PPE Division, CERN, Geneva, Switzerland |
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 5·106 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 µg 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 149Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach. |