LABELING 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 (In-111)-BLMC) and (InCl3)-I n-111 in three squamous cell cancer (SCC) cell lines. Material and met hods: Three recently established SCC cell lines were investigated usin g the 96-well clonogenic assay. Concentrations causing 50% inhibition in cell survival (IC50) were calculated for BLM and two specific activ ities of In-111-BLMC (40 MBq/mg BLM (low) and 195 MBq/mg BLM (high)). Results: In-111-BLMC (low) was the most toxic to the SCC cell lines. I n-111-BLMC containing 4.9-fold more activity of In-111 (195 MBq/mg BLM ) was more effective than BLM (p = 0.0029). but not as toxic as In-111 -BLMC (low) (p = 0.0023). UT-SCC-19A had a IC50 value for BLM as low a s 4.1 nM, whereas IC50 values for In-111-BLMC (low) and In-111-BLMC (h igh) were 2.0 nM and 2.6 nM, respectively. The most chemoresistant cel l line UT-SCC-12A had a IC50 value for BLM of 18.8 nM, for In-111-BLMC (low) 10.7 nM and for In-111-BLMC (high) 12.7 nM. (InCl3)-In-111 had no cell killing effect. Conclusions: This study shows that In-111-BLMC is superior in SCC cell killing compared with BLM. These data provide the basis for further clinical investigations of In-111-BLMC.