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
Nema prikaza
Autori
Miederer, MSeidl, C
Beyer, GJ
Charlton, DE
Vranješ-Đurić, Sanja
Čomor, Jožef J.
Huber, R
Nikula, T
Apostolidis, C
Schuhmacher, C
Becker, KF
Senekowitsch-Schmidtke, R
Članak u časopisu
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 d...etermined 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.
Izvor:
Radiation Research, 2003, 159, 5, 612-620
DOI: 10.1667/0033-7587(2003)159[0612:COTROT]2.0.CO;2
ISSN: 0033-7587
PubMed: 12710872
WoS: 000182629400005
Scopus: 2-s2.0-0037964241
Kolekcije
Institucija/grupa
VinčaTY - 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 . .