TY  - JOUR
AU  - Miederer, M
AU  - Seidl, C
AU  - Beyer, GJ
AU  - Charlton, DE
AU  - Vranješ-Đurić, Sanja
AU  - Čomor, Jožef J.
AU  - Huber, R
AU  - Nikula, T
AU  - Apostolidis, C
AU  - Schuhmacher, C
AU  - Becker, KF
AU  - Senekowitsch-Schmidtke, R
PY  - 2003
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/2630
AB  - We investigated the effects of the a-particle emitters Tb-149 and Bi-213 coupled to a tumor-specific antibody targeting the mutated delta 9 E-cadherin (d9 E-Cad) on single cells and cell pellets. The d9 mutation of the adhesion molecule E-cadherin is found in 10% of diffuse-type gastric cancers and is not expressed in normal tissue. Human breast cancer cells (MDA-MB-435S) transfected with d9 E-Cad or the wild-type E-cadherin gene were used to study the effects of anti-d9 E-Cad MAb coupled to Tb-149 and Bi-213 (Tb-149-d9 MAb and Bi-213-d9 MAb). The density of binding sites determined on transfected MDA tumor cells by Scatchard analysis and flow cytometry varied from 4 x 10(4) to 6 x 10(4) antigens per cell. Internalization of radioimmunoconjugates by cells expressing d9 E-Cad was less than 10% of bound antibody within 240 min. The effect of the radioimmunoconjugates on cell suspensions and cell pellets was quantified by [H-3]thymidine incorporation, and the dose to the cell nuclei was determined using microdosimetric calculations. Tb-149 and Bi-213 immunoconjugates affected cells in suspension similarly. Significant differences in the proliferation capacity of d9 E-cadherin- and wildtype E-cadherin-expressing cells were observed at activity concentrations around 185 kBq/ml, corresponding to antibody concentrations between 200 ng/ml and 1000 ng/ml. Proliferation after incubation with Bi-213-d9 MAb was 50% greater in pelleted wild-type E-Cad-expressing cells compared to wildtype E-Cad cells in suspension. In contrast, the proliferation of pelleted d9 E-Cad cells was similar to that of d9 E-Cad cells in suspension. For Tb-149-d9 MAb, no significant difference was found between pelleted cells and cells in suspension for low activity concentrations. However, at high activity concentrations, Tb-149-d9 MAb had only a small effect on pelleted cells. These in vitro studies demonstrate different effects of Tb-149 and Bi-213 conjugated to a tumor-specific antibody toward single cells and tumor cell pellets. Microdosimetric simulation of single cell survival after a-particle irradiation modeled the experimental results with reasonable accuracy. (C) 2003 by Radiation Research Society.
T2  - Radiation Research
T1  - Comparison of the radiotoxicity of two alpha-particle-emitting immunoconjugates, terbium-149 and bismuth-213, directed against a tumor-specific, exon 9 deleted (d9) E-cadherin adhesion protein
VL  - 159
IS  - 5
SP  - 612
EP  - 620
DO  - 10.1667/0033-7587(2003)159[0612:COTROT]2.0.CO;2
ER  - 

@article{
author = "Miederer, M and Seidl, C and Beyer, GJ and Charlton, DE and Vranješ-Đurić, Sanja and Čomor, Jožef J. and Huber, R and Nikula, T and Apostolidis, C and Schuhmacher, C and Becker, KF and Senekowitsch-Schmidtke, R",
year = "2003",
abstract = "We investigated the effects of the a-particle emitters Tb-149 and Bi-213 coupled to a tumor-specific antibody targeting the mutated delta 9 E-cadherin (d9 E-Cad) on single cells and cell pellets. The d9 mutation of the adhesion molecule E-cadherin is found in 10% of diffuse-type gastric cancers and is not expressed in normal tissue. Human breast cancer cells (MDA-MB-435S) transfected with d9 E-Cad or the wild-type E-cadherin gene were used to study the effects of anti-d9 E-Cad MAb coupled to Tb-149 and Bi-213 (Tb-149-d9 MAb and Bi-213-d9 MAb). The density of binding sites determined on transfected MDA tumor cells by Scatchard analysis and flow cytometry varied from 4 x 10(4) to 6 x 10(4) antigens per cell. Internalization of radioimmunoconjugates by cells expressing d9 E-Cad was less than 10% of bound antibody within 240 min. The effect of the radioimmunoconjugates on cell suspensions and cell pellets was quantified by [H-3]thymidine incorporation, and the dose to the cell nuclei was determined using microdosimetric calculations. Tb-149 and Bi-213 immunoconjugates affected cells in suspension similarly. Significant differences in the proliferation capacity of d9 E-cadherin- and wildtype E-cadherin-expressing cells were observed at activity concentrations around 185 kBq/ml, corresponding to antibody concentrations between 200 ng/ml and 1000 ng/ml. Proliferation after incubation with Bi-213-d9 MAb was 50% greater in pelleted wild-type E-Cad-expressing cells compared to wildtype E-Cad cells in suspension. In contrast, the proliferation of pelleted d9 E-Cad cells was similar to that of d9 E-Cad cells in suspension. For Tb-149-d9 MAb, no significant difference was found between pelleted cells and cells in suspension for low activity concentrations. However, at high activity concentrations, Tb-149-d9 MAb had only a small effect on pelleted cells. These in vitro studies demonstrate different effects of Tb-149 and Bi-213 conjugated to a tumor-specific antibody toward single cells and tumor cell pellets. Microdosimetric simulation of single cell survival after a-particle irradiation modeled the experimental results with reasonable accuracy. (C) 2003 by Radiation Research Society.",
journal = "Radiation Research",
title = "Comparison of the radiotoxicity of two alpha-particle-emitting immunoconjugates, terbium-149 and bismuth-213, directed against a tumor-specific, exon 9 deleted (d9) E-cadherin adhesion protein",
volume = "159",
number = "5",
pages = "612-620",
doi = "10.1667/0033-7587(2003)159[0612:COTROT]2.0.CO;2"
}

Miederer, M., Seidl, C., Beyer, G., Charlton, D., Vranješ-Đurić, S., Čomor, J. J., Huber, R., Nikula, T., Apostolidis, C., Schuhmacher, C., Becker, K.,& Senekowitsch-Schmidtke, R.. (2003). Comparison of the radiotoxicity of two alpha-particle-emitting immunoconjugates, terbium-149 and bismuth-213, directed against a tumor-specific, exon 9 deleted (d9) E-cadherin adhesion protein. in Radiation Research, 159(5), 612-620.
https://doi.org/10.1667/0033-7587(2003)159[0612:COTROT]2.0.CO;2

Miederer M, Seidl C, Beyer G, Charlton D, Vranješ-Đurić S, Čomor JJ, Huber R, Nikula T, Apostolidis C, Schuhmacher C, Becker K, Senekowitsch-Schmidtke R. Comparison of the radiotoxicity of two alpha-particle-emitting immunoconjugates, terbium-149 and bismuth-213, directed against a tumor-specific, exon 9 deleted (d9) E-cadherin adhesion protein. in Radiation Research. 2003;159(5):612-620.
doi:10.1667/0033-7587(2003)159[0612:COTROT]2.0.CO;2 .

Miederer, M, Seidl, C, Beyer, GJ, Charlton, DE, Vranješ-Đurić, Sanja, Čomor, Jožef J., Huber, R, Nikula, T, Apostolidis, C, Schuhmacher, C, Becker, KF, Senekowitsch-Schmidtke, R, "Comparison of the radiotoxicity of two alpha-particle-emitting immunoconjugates, terbium-149 and bismuth-213, directed against a tumor-specific, exon 9 deleted (d9) E-cadherin adhesion protein" in Radiation Research, 159, no. 5 (2003):612-620,
https://doi.org/10.1667/0033-7587(2003)159[0612:COTROT]2.0.CO;2 . .