INCREASED DELIVERY OF A NEW CISPLATIN ANALOG (254-S) IN A RAT-BRAIN TUMOR BY AN INTRACAROTID INFUSION OF BRADYKININ

The intracarotid infusion of bradykinin has been shown to selectively increase capillary permeability in a brain tumor without affecting eit her normal brain capillary permeability or the systemic blood pressure . We examined whether the intracarotid infusion of bradykinin could se lectively increase the delivery of a new watersoluble antitumor agent, cis-diammine glycolato-platinum (254-S, 303.2 mel. wt.), to transplan ted RG2 glioma in rats. The platinum contents in the brain, tumor tiss ues and plasma were measured using an atomic absorption spectrophotome ter. The transfer ratio of 254-S rom plasma to the tissues was calcula ted and expressed as the volume of plasma containing platinum per g ti ssue (Dp, mu l g(-1)). Intracarotid bradykinin infusion at a rate of 2 0 mu g kg(-1) min(-1) increased the delivery of 254-S in the tumor tis sue by 1.3-fold when compared with intracarotid infusion of 0.9% salin e (48.78 +/- 18.11 vs. 37.12 +/- 12.53; p < 0.05). In normal brain tis sue including the ipsilateral cortex, the contralateral basal ganglia and the contralateral cortex, bradykinin did not significantly increas e the delivery of 254-S in comparison with 0.9% saline (12.28 +/- 9.53 vs. 10.70 +/- 5.05, 4.96 +/- 3.54 vs 4.96 +/- 4.80, 7.64 +/- 4.10 vs. 13.07 +/- 11.38, respectively). These results indicate that the intra carotid infusion of bradykinin selectively increases the delivery of 2 54-S to the brain tumor without affecting the normal brain. This metho d may, therefore, enhance the antitumor effect of 254-S for the treatm ent of brain tumors and also reduce neurotoxicity in the normal brain.