In vitro release of SM-11355, cis[((1R,2R)-1,2-cyclohexanediamine-N,N ')bis(myristato)] platinum(II) suspended in lipiodol

SM-11355, cis[((1R,2R)-1,2-cyclohelanediamine-N,N')bis(myristato)] platinum (II) is a lipophilic platinum complex, SM-11355 suspended in Lipiodol (SM-1 1355/Lipiodol) was previously shown to have antitumor effects against rat h epatic tumors after intra-arterial administration. In the present study, th e in vitro release of platinum compounds from SM-11355/Lipiodol was examine d. A test tube containing 10 ml of saline and 1 ml of SM-11355/Lipiodol was rotated at 5 rpm in a vertical orientation. The platinum concentration in saline gradually increased for 28 d. From HPLC analysis, cyclohexane-1,2-di amineplatinum(II) dichloride (DPC) and cyclohexane-1,2-diamineplatinum(II) chloroiodide (DPCI) were detected in the saline, and the sum of these two c ompounds was equivalent to the total platinum amount in the saline determin ed by atomic absorption spectrophotometry at days 21 and 28, DPC showed sig nificant growth inhibitory activities, with IC50 values of 0.1-0.7 nmol/ml in rat hepatoma AH-109A cells and 5 human tumor cell lines, as effective as cisplatin, These findings suggest that SM-11355/Lipiodol exerts antitumor effects by releasing active platinum compounds, and that DPC is one of the candidates of the active compounds.