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Labelling of bleomycin with Auger-emitter increases cytotoxicity in squamous-cell cancer cell lines
H A Jääskelä-Saari1, K J Kairemo, H A Ramsay
1Department of Otorhinolaryngology, Helsinki University Central Hospital, Finland.
Purpose:
To investigate the cytotoxicity of bleomycin (BLM), two Auger-emitting bleomycin complexes (indium-111 ((111)In)-BLMC) and (111)InCl3 in three squamous cell cancer (SCC) cell lines.
Material And Methods:
Three recently established SCC cell lines were investigated using the 96-well clonogenic assay. Concentrations causing 50% inhibition in cell survival (IC50) were calculated for BLM and two specific activities of (111)In-BLMC (40 MBq/mg BLM (low) and 195 MBq/mg BLM (high)).
Results:
(111)In-BLMC (low) was the most toxic to the SCC cell lines. (111)In-BLMC containing 4.9-fold more activity of (111)In (195 MBq/mg BLM) was more effective than BLM (p=0.0029), but not as toxic as (111)In-BLMC (low) (p=0.0023). UT-SCC-19A had a IC50 value for BLM as low as 4.1 nM, whereas IC50 values for (111)In-BLMC (low) and (111)In-BLMC (high) were 2.0 nM and 2.6 nM, respectively. The most chemoresistant cell line UT-SCC-12A had a IC50 value for BLM of 18.8 nM, for (111)In-BLMC (low) 10.7 nM and for (111)In-BLMC (high) 12.7 nM. (111)InCl3 had no cell killing effect.
Conclusions:
This study shows that (111)In-BLMC is superior in SCC cell killing compared with BLM. These data provide the basis for further clinical investigations of (111)In-BLMC.