In vitro effects of free 211At,211At-albumin and 211At-monoclonal antibody compared to external photon irradiation on two human cancer cell lines.
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.
Palm
S
S
Department of Radiation Physics, Göteborg University, Sahlgrenska University Hospital, Sweden. stig.palm@radfys.gu.se
Andersson
H
H
Bäck
T
T
Claesson
I
I
Delle
U
U
Hultborn
R
R
Jacobsson
L
L
Köpf
I
I
Lindegren
S
S
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
D000911:Antibodies, Monoclonal; D019275:Radiopharmaceuticals; D001246:Astatine