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: G-J Beyer, M Miederer, S Vranjes-Durić, J J Comor, G Künzi, O Hartley, R Senekowitsch-Schmidtke, D Soloviev, F Buchegger
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 31 Issue 4 Pg. 547-54 (Apr 2004) ISSN: 1619-7070 [Print] Germany
• PMID: 14722680 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents
• Radiopharmaceuticals
• terbium-rituximab
• Rituximab

Topics

• 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
• Rituximab
• Survival
• Tissue Distribution
• Treatment Outcome