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

Details

Serval ID
serval:BIB_12CE549A1E8F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab
Journal
European Journal of Nuclear Medicine and Molecular Imaging
Author(s)
Beyer  G. J., Miederer  M., Vranjes-Duric  S., Comor  J. J., Kunzi  G., Hartley  O., Senekowitsch-Schmidtke  R., Soloviev  D., Buchegger  F.
ISSN
1619-7070 (Print)
Publication state
Published
Issued date
04/2004
Volume
31
Number
4
Pages
547-54
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
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 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
Pubmed
Web of science
Create date
25/01/2008 11:27
Last modification date
20/08/2019 12:41
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