Antitumor activity and tissue distribution of bis(bilato)-1,2-cyclohexanediammineplatinum(II) complexes in BDF1 mice...

Murine reticulum cell sarcoma (M5076) was subcutaneously implanted into BDF1 mice and then the antitumor activity of seven micelle-forming type platinum complexes was tested. The antitumor activity of bis(hyodeoxycholato)-trans-(+/-)-1,2-cyclohexanediammineplatinu m(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, 2-cyclohexanediammineplatinum(II)(t(c)-DACHP-(cheno)2) (49% inhibition) and bis(ursodeoxy-cholato)-trans(+/-)-1,2-cyclohexanediammine platinum (II) (t-DACHP(urso)2) (48% inhibition). t-DACHP(hyo)2 and t-DACHP(urso)2 inhibited sarcoma 180 growth (63% and 33%, respectively). The organ distribution of the complex with the highest antitumor activity was compared with that of a complex with negligible antitumor activity. The total Pt levels were significantly higher in tumor tissue from mice given the more active complex 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.