Title: Alpha-particle emitting 213Bi-anti-EGFR immunoconjugates eradicate tumor cells independent of oxygenation
Authors: WULBRAND ChristianSEIDL C.GAERTNER F. C.BRUCHERTSEIFER FrankMORGENSTERN AlfredESSLER M.SENEKOWITSCH-SCHMIDTKE R.
Citation: PLOS ONE vol. 8 no. 5 p. e64730
Publisher: PUBLIC LIBRARY SCIENCE
Publication Year: 2013
JRC N°: JRC73780
ISSN: 1932-6203
URI: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0064730
http://publications.jrc.ec.europa.eu/repository/handle/JRC73780
DOI: 10.1371/journal.pone.0064730
Type: Articles in periodicals and books
Abstract: Hypoxia is a central problem in tumor treatment because hypoxic cells are less sensitive to chemo- and radiotherapy than normoxic cells. Radioresistance of hypoxic tumor cells is due to reduced sensitivity towards low Linear Energy Transfer (LET) radiation. High LET α-emitters are thought to eradicate tumor cells independent of cellular oxygenation. Therefore, the aim of this study was to demonstrate that the cell-bound α-particle emitting 213Bi immunoconjugates efficiently kill hypoxic just like normoxic CAL33 tumor cells. For that purpose CAL33 cells were incubated with 213Bianti- EGFR-MAb or irradiated with photons with a nominal energy of 6 MeV both under hypoxic and normoxic conditions. Oxygenation of cells was checked via the hypoxia-associated marker HIF-1α. Survival of cells was analysed using the clonogenic assay. Cell viability was monitored with the WST colorimetric assay. Results were evaluated statistically using a t-test and a Generalized Linear Mixed Model (GLMM). Survival and viability of CAL33 cells decreased both after incubation with increasing 213Bi-anti-EGFR-MAb activity concentrations (9.25 kBq/ml – 1.48 MBq/ml) and irradiation with increasing doses of photons (0.5 – 12 Gy). Following photon irradiation survival and viability of normoxic cells were significantly lower than those of hypoxic cells at all doses analysed. In contrast, cell death induced by 213Bianti- EGFR-MAb turned out to be independent of cellular oxygenation. These results demonstrate for the first time that α-particle emitting 213Bi-immunoconjugates eradicate hypoxic tumor cells as effective as normoxic cells. Therefore, 213Biradioimmunotherapy seems to be an appropriate strategy for treatment of hypoxic tumors.
JRC Directorate:Nuclear Safety and Security

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