Labelling of bleomycin with Auger-emitter increases cytotoxicity in squamous-cell cancer cell lines

Purpose: To investigate the cytotoxicity of bleomycin (BLM), two Auger-emitting bleomycin complexes (indium-111 (111In)-BLMC) and 111InCl3 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 (IC) were calculated for BLM and two specific activities of 111In BLMC (40 MBq/mg BLM (low) and 195 MBq/mg BLM (high)). Results: 111In-BLMC (low) was the most toxic to the SCC cell lines. 111In-BLMC containing 4.9-fold more activity of 111In (195 MBq/mg BLM) was more effective than BLM (p=0.0029), but not as toxic as 111In-BLMC (low) (p=0.0023). UT-SCC-19A had a IC50 value for BLM as low as 4.1 nm, whereas IC50 values for 111In-BLMC (low) and 111In-BLMC (high) were 2.0 nm and 2.6 nm, respectively. The most chemoresistant cell line UT-SCC-12A had a IC value for BLM of 18.8 nm, for 111In50 BLMC (low) 10.7 nm and for 111In-BLMC (high) 12.7 nm. 111InCl3 had no cell killing effect. Conclusions: This study shows that 111In-BLMC is superior in SCC cell killing compared with BLM. These data provide the basis for further clinical investigations of 111In-BLMC.