Cytotoxic effects of I-125-labeled PBZr ligand PK 11195 in prostatic tumorcells: therapeutic implications

The effect of [I-125]PK 11195 was examined in human prostatic tumor cells ( DU 145) in culture and compared with Na[I-125] and non-radioactive PK 11195 , [I-125]PK 11195 was clearly cytocidal. The data for dose-related cell sur vival with [I-125]PK 11195 showed a linear relationship. Na[I-125] or non-l abeled PK 11195 at similar concentrations did not lead to any cell killing. The uptake of [I-125]PK 11195 and [H-3]PK 11195 in cells was very similar. Fragmentation of DNA measured by agarose gel electrophoresis showed that e xposure of DU 145 cells to [I-125]PK 11195 for 1, 4 or 24 h caused no fragm entation. These results indicate that nuclear DNA is not the prime binding site for [I-125]PK 11195, which is consistent with the presence of specific peripheral benzodiazepine receptors (PBZr) in the mitochondria. The cell k illing effect of [I-125]PK 11195 suggests the use of PBZr ligand for radiot herapy. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.