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Eur J Nucl Med Mol Imaging. 2004 Apr;31(4):547-54. Epub 2004 Jan 14.

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

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  • 1Division of Nuclear Medicine, University Hospital of Geneva, 24 Rue Micheli du Crest, 1211 Geneva 14, Switzerland. gerd.beyer@hcuge.ch

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.

PMID:
14722680
[PubMed - indexed for MEDLINE]
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