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Exposure of human osteosarcoma and bone marrow cells to tumour-targeted alpha-particles and gamma-irradiation: analysis of cell survival and microdosimetry.

Publication ,  Journal Article
Aurlien, E; Larsen, RH; Akabani, G; Olsen, DR; Zalutsky, MR; Bruland, OS
Published in: Int J Radiat Biol
August 2000

PURPOSE: This study was designed to compare the cytotoxic effects of an alpha-emitting radioimmunoconjugate, which binds to osteosarcoma but not to bone marrow cells, with those of external gamma-irradiation. MATERIALS AND METHODS: The human osteosarcoma cell line, OHS-s1, and mononuclear cells from bone marrow (BM) harvested from healthy donors, were used for these experiments. Cells in suspension were added to various activity concentrations of the anti-osteosarcoma monoclonal antibody TP-3 radiolabelled with 211At. Following incubation for 1 h, unbound radioactivity was washed off and cell survival was determined from clonogenic assays. Microdosimetry was calculated based on binding and retention kinetics of 211At to the cells, as well as cellular and nuclear diameters. For comparison, cell suspensions were irradiated with a single dose of 60Co gamma-rays. RESULTS: 211At-labelled TP-3 showed heterogeneous binding to OHS-s1 cells, with a considerable variation among experiments. About 78% of the initially bound 211At decayed while associated with the OHS-s1 cells. D0 values estimated by microdosimetry were 0.33 (0.22-0.48, range) Gy and 1.18 (0.89-1.89) Gy for OHS-s1 and BM cells, respectively, whereas D0 values after external beam irradiation were 0.86+/-0.07Gy and 1.71+/-0.22Gy. The relative biological effectiveness (RBE) of 211At-labelled TP-3 at 37% survival was 3.43 for OHS-s1 and 1.55 for BM. CONCLUSIONS: High-LET targeted alpha-particle exposure killed osteosarcoma cells more effectively than bone marrow cells, although heterogeneous antigen expression among these tumour cells limited the magnitude of this effect.

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Published In

Int J Radiat Biol

DOI

ISSN

0955-3002

Publication Date

August 2000

Volume

76

Issue

8

Start / End Page

1129 / 1141

Location

England

Related Subject Headings

  • X-Rays
  • Tumor Cells, Cultured
  • Osteosarcoma
  • Oncology & Carcinogenesis
  • Humans
  • Dose-Response Relationship, Radiation
  • Cell Survival
  • Bone Marrow Cells
  • Alpha Particles
  • 3404 Medicinal and biomolecular chemistry
 

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Aurlien, E., Larsen, R. H., Akabani, G., Olsen, D. R., Zalutsky, M. R., & Bruland, O. S. (2000). Exposure of human osteosarcoma and bone marrow cells to tumour-targeted alpha-particles and gamma-irradiation: analysis of cell survival and microdosimetry. Int J Radiat Biol, 76(8), 1129–1141. https://doi.org/10.1080/09553000050111604
Aurlien, E., R. H. Larsen, G. Akabani, D. R. Olsen, M. R. Zalutsky, and O. S. Bruland. “Exposure of human osteosarcoma and bone marrow cells to tumour-targeted alpha-particles and gamma-irradiation: analysis of cell survival and microdosimetry.Int J Radiat Biol 76, no. 8 (August 2000): 1129–41. https://doi.org/10.1080/09553000050111604.
Aurlien E, Larsen RH, Akabani G, Olsen DR, Zalutsky MR, Bruland OS. Exposure of human osteosarcoma and bone marrow cells to tumour-targeted alpha-particles and gamma-irradiation: analysis of cell survival and microdosimetry. Int J Radiat Biol. 2000 Aug;76(8):1129–41.
Aurlien, E., et al. “Exposure of human osteosarcoma and bone marrow cells to tumour-targeted alpha-particles and gamma-irradiation: analysis of cell survival and microdosimetry.Int J Radiat Biol, vol. 76, no. 8, Aug. 2000, pp. 1129–41. Pubmed, doi:10.1080/09553000050111604.
Aurlien E, Larsen RH, Akabani G, Olsen DR, Zalutsky MR, Bruland OS. Exposure of human osteosarcoma and bone marrow cells to tumour-targeted alpha-particles and gamma-irradiation: analysis of cell survival and microdosimetry. Int J Radiat Biol. 2000 Aug;76(8):1129–1141.
Journal cover image

Published In

Int J Radiat Biol

DOI

ISSN

0955-3002

Publication Date

August 2000

Volume

76

Issue

8

Start / End Page

1129 / 1141

Location

England

Related Subject Headings

  • X-Rays
  • Tumor Cells, Cultured
  • Osteosarcoma
  • Oncology & Carcinogenesis
  • Humans
  • Dose-Response Relationship, Radiation
  • Cell Survival
  • Bone Marrow Cells
  • Alpha Particles
  • 3404 Medicinal and biomolecular chemistry