Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab

Beyer, Gerd-Jurgen; Miederer, M; Vranjes-Durić, S; Comor, J J; Kuenzi, Gabriel; Hartley, Oliver; Senekowitsch-Schmidtke, R; Soloviev, D; Buchegger, Franz

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Title		Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab
Authors		Beyer, Gerd-Jurgen Miederer, M Vranjes-Durić, S Comor, J J Kuenzi, Gabriel Hartley, Oliver Senekowitsch-Schmidtke, R Soloviev, D Buchegger, Franz show all authors [1 - 9]
Published in		European Journal of Nuclear Medicine and Molecular Imaging. 2004, vol. 31, no. 4, p. 547-54
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.
Keywords		Alpha Particles/therapeutic use — Animals — Antibodies — Monoclonal/pharmacokinetics/therapeutic use — Antibodies — Monoclonal — Murine-Derived — Antineoplastic Agents/therapeutic use — Apoptosis/radiation effects — Cell Line — Tumor — Cell Survival/radiation effects — Dose-Response Relationship — Drug — Drug Delivery Systems/methods — Evidence-Based Medicine/methods — Female — Leukemia/drug therapy/metabolism/radiotherapy — Mice — Mice — SCID — Organ Specificity — Radioimmunotherapy/methods — Radiopharmaceuticals/therapeutic use — Reproducibility of Results — Survival — Tissue Distribution — Treatment Outcome
Identifiers		DOI: 10.1007/s00259-003-1413-9 PMID: 14722680
Full text		Article (Published version) (329 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale
Research group		HIV (835)
Citation (ISO format)		BEYER, Gerd-Jurgen et al. Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab. In: European Journal of Nuclear Medicine and Molecular Imaging, 2004, vol. 31, n° 4, p. 547-54. https://archive-ouverte.unige.ch/unige:26051