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

Miederer, M
Vranjes-Durić, S
Comor, J J
Senekowitsch-Schmidtke, R
Soloviev, D
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Published in European journal of nuclear medicine and molecular imaging. 2004, vol. 31, no. 4, p. 547-54
Collection Open Access - Licence nationale Springer
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 useAnimalsAntibodiesMonoclonal/pharmacokinetics/therapeutic useAntibodiesMonoclonalMurine-DerivedAntineoplastic Agents/therapeutic useApoptosis/radiation effectsCell LineTumorCell Survival/radiation effectsDose-Response RelationshipDrugDrug Delivery Systems/methodsEvidence-Based Medicine/methodsFemaleLeukemia/drug therapy/metabolism/radiotherapyMiceMiceSCIDOrgan SpecificityRadioimmunotherapy/methodsRadiopharmaceuticals/therapeutic useReproducibility of ResultsSurvivalTissue DistributionTreatment Outcome
PMID: 14722680
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Research group HIV (835)
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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. doi: 10.1007/s00259-003-1413-9 https://archive-ouverte.unige.ch/unige:26051

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Deposited on : 2013-01-30

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