Extensive chemical degradation of bleomycin during attempted labelling with 51-Cr

Labelling of the cytostatic agent bleomycin with 51-Cr and use of the product for biodistribution studies have been reported in the literature. The labelling procedure involves incubation for 40 min at 130 degrees C. Since bleomycins are polar glycopeptides sensitive to hydrolytic cleavage we were concerned about possible degradation of the drug during these unfavourable conditions. We have therefore investigated the stability of bleomycin as a function of temperature and pH of the solution and attempted to achieve the maximum labelling efficiency with minimal degradation of the two principal bleomycin components.

The chemical stability of unlabelled bleomycin was investigated under labelling conditions at 130 degrees C and in buffer of pH 1-6 at room temperature (23 degrees C) and 60 degrees C. The samples were assayed by high-performance liquid chromatography (HPLC). The labelling efficiency of the 51-Cr-bleomycin complex was determined by thin layer chromatography and activity measurement with a high pure Germanium (HPGe)-detector at various incubation temperatures and times.

Comparisons of rates of degradation of bleomycin with labelling efficiency as functions of temperature and time showed that under no condition could satisfactory labelling (> 97%) be obtained without considerable degradation of bleomycin.

Labelling of bleomycin with 51-Cr does not yield a product suitable for investigations in patients.