ANTITUMOR-ACTIVITY AND TISSUE DISTRIBUTION OF BIS(BILATO)-1,2-CYCLOHEXANEDIAMMINEPLATINUM(II) COMPLEXES IN BDF(1) MICE WITH MURINE RETICULUM-CELL SARCOMA (M5076)

Murine reticulum cell sarcoma (M5076) was subcutaneously implanted int o BDF1 mice and then the antitumor activity of seven micelle-forming t ype platinum complexes was tested. The antitumor activity of 1,2-cyclo hexanediammineplatinum(II)(t-DACHP(hyo)2) was highest (95% inhibition of growth), and it was dose dependent with a large therapeutic index. This was followed by bis(chenodeoxycholato)-trans(+/-)(cis)-1, clohexa nediammineplatinum(II)(t(c)-DACHP-(cheno)2) (49% inhibition) and holat o)-trans(+/-)-1,2-cyclohexanediammineplatinum (II) (t-DACHP(urso)2) (4 8% inhibition). t-DACHP(hyo)2 and t-DACHP(urso)2 inhibited sarcoma 180 growth (63% and 33%, respectively). The organ distribution of the com plex with the highest antitumor activity was compared with that of a c omplex with negligible antitumor activity. The total Pt levels were si gnificantly higher in tumor tissue from mice given the more active com plex than in tumor tissue from mice given the less active complex. Pt levels in the kidney and the spleen showed a similar pattern, but the lung tissue Pt levels were significantly higher in mice given the less active complex.