en
Scientific article
Open access
English

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

Published inEuropean journal of nuclear medicine and molecular imaging, vol. 31, no. 4, p. 547-554
Collection
  • Open Access - Licence nationale Springer
Publication date2004
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
Research group
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. 547–554. doi: 10.1007/s00259-003-1413-9
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal1619-7070
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359downloads

Technical informations

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