title: In vitro effects of free 211At,211At-albumin and 211At-monoclonal antibody compared to external photon irradiation on two human cancer cell lines.
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.
  
  
  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.
authors.affiliation: Department of Radiation Physics, Göteborg University, Sahlgrenska University Hospital, Sweden. stig.palm@radfys.gu.se
authors.forename: S
authors.initials: S
authors.lastname: Palm
authors.forename: H
authors.initials: H
authors.lastname: Andersson
authors.forename: T
authors.initials: T
authors.lastname: Bäck
authors.forename: I
authors.initials: I
authors.lastname: Claesson
authors.forename: U
authors.initials: U
authors.lastname: Delle
authors.forename: R
authors.initials: R
authors.lastname: Hultborn
authors.forename: L
authors.initials: L
authors.lastname: Jacobsson
authors.forename: I
authors.initials: I
authors.lastname: Köpf
authors.forename: S
authors.initials: S
authors.lastname: Lindegren
mesh_terms: D000911:Antibodies, Monoclonal; D001246:Astatine / Q000493:pharmacokinetics / Q000633:toxicity*; D002455:Cell Division / Q000528:radiation effects; D002467:Cell Nucleus / Q000473:pathology / Q000528:radiation effects / Q000648:ultrastructure; D048429:Cell Size / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects*; D003110:Colonic Neoplasms; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms; D017785:Photons; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D019275:Radiopharmaceuticals; D001246:Astatine