Chemical properties and tumor affinity of separated isomers of cobalt-bleomycin.

Abstract

Co-57 bleomycin is a chemically stable and diagnostically useful radiopharmaceutical. Stoichiometric preparation of Co-bleomycin causes two chemically different complexes. Four kinds of chelates (A2- type I, A2-type II, B2-type I and B2-type II) are easily separated by silicagel then-layer chromatography. Circular dicroism study of these chelates indicate that two types of complexes are conformational isomers. This chemical difference is assumed to cause the difference in the biological behavior. The biodistribution study of each type of complex, using tumor-bearing mice, showed higher tumor-to-blood ratios and tumor-to muscle ratios as compared with the clinical grade Co-bleomycin mixture. But the difference between the two types was not as large as expected. The similarity in biologic bahavior suggests that the groups on the bleomycin molecule, which are concerned with chelate formation, do not take part in its binding to DNA.