Targeted alpha therapy in vivo: Direct evidence for single cancer cell kill using 149Tb-rituximab Journal Article
| Authors: | Beyer, G. J.; Miederer, M.; Vranješ-Durić, S.; Čomor, J. J.; Künzi, G.; Hartley, O.; Senekowitsch-Schmidtke, R.; Soloviev, D.; Buchegger, F. |
| Article Title: | 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 5.106 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 μg 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 149Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach. |
| Keywords: | survival; controlled study; treatment outcome; leukemia; unclassified drug; nonhuman; antineoplastic agents; rituximab; radiopharmaceuticals; evidence-based medicine; reproducibility of results; animal cell; mouse; animals; mice; animal tissue; cell survival; apoptosis; animal experiment; animal model; in vivo study; dose-response relationship, drug; mice, scid; cell line, tumor; drug delivery systems; liver; antibodies, monoclonal; tissue distribution; cancer cell; lymphoma; organ specificity; gene therapy; graft survival; radioisotope; radioimmunotherapy; combined immunodeficiency; concentration response; cell killing; spleen cell; leukaemia; antibody conjugate; alpha particles; bone tissue; cd20 antibody; terbium 149; terbium; female; article; alpha particle-emitting radionuclides; radio-immunotherapy; terbium-149; daudi cell |
| Journal Title: | European Journal of Nuclear Medicine and Molecular Imaging |
| Volume: | 31 |
| Issue: | 4 |
| ISSN: | 1619-7070 |
| Publisher: | Springer |
| Date Published: | 2004-04-01 |
| Start Page: | 547 |
| End Page: | 554 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 14722680 |
| DOI: | 10.1007/s00259-003-1413-9 |
| DOI/URL: | |
| Notes: | Eur. J. Nucl. Med. Mol. Imaging -- Cited By (since 1996):28 -- Export Date: 16 June 2014 -- CODEN: EJNMA C2 - 14722680 -- Source: Scopus |
