In vitro effects of free 211At,211At-albumin and 211At-monoclonal antibody compared to external photon irradiation on two human cancer cell lines

Anticancer Res. 2000 Mar-Apr;20(2A):1005-12.

Abstract

Background: The aim of this study was to perform various 211At irradiations of importance for the evaluation of 211At-radioimmunotherapy, and compare the effect with that of low linear energy transfer (LET) radiation.

Materials and methods: All irradiations were performed on low-concentration single-cell suspensions. Growth assays using 96-well plates were used to estimate apparent cell survival. Centrifuge tube filters were used to estimate the cell uptake and binding of 211At.

Results: A relative biological effect (RBE) of 12 +/- 2 (Colo-205) and 5.3 +/- 0.7 (OVCAR-3) was found from 211At-albumin irradiations. There was a 174 +/- 28 times higher free 211At concentration in the cell fraction than in the surrounding medium. For 211At-MAb, an 8,000-30,000 times higher concentration in the cell fraction was achieved, compared to the medium. Corrected for the uptake, an average of 31 +/- 2 ([211At]-astatine) or 26 +/- 5 ([211At]-MAb) decays per cell were required for 37% survival of Colo-205 cells. An average of 19 +/- 3 decays ([211At]-astatine) were required per OVCAR-3 cell.

Conclusions: Cell uptake and binding of 211At was unexpectedly high, possibly favouring its therapeutic use. The binding is probably to the cell surface. The RBE is 5.3 +/- 0.7 for OVCAR-3 and 12 +/- 2 for Colo-205 cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Astatine / pharmacokinetics
  • Astatine / toxicity*
  • Cell Division / radiation effects
  • Cell Nucleus / pathology
  • Cell Nucleus / radiation effects
  • Cell Nucleus / ultrastructure
  • Cell Size / radiation effects
  • Cell Survival / radiation effects*
  • Colonic Neoplasms
  • Female
  • Humans
  • Ovarian Neoplasms
  • Photons
  • Radioimmunotherapy
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / toxicity*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Radiopharmaceuticals
  • Astatine