INTRAVENOUS RMP-7 SELECTIVELY INCREASES UPTAKE OF CARBOPLATIN INTO RAT-BRAIN TUMORS

Rats implanted with RG-2 gliomas were administered i.v, RMP-7 and [C-1 4]carboplatin. Changes in the permeability of the blood-brain barrier to carboplatin were determined using quantitative autoradiography, i.v . infusions of RMP-7 induced an increase in the permeability of the va scular barrier within the tumor to carboplatin. Additionally, permeabi lity of brain tissue proximal to, but clearly outside the tumor mass, was also increased. Progressively less uptake of [C-14]carboplatin was observed as distance from the tumor border increased. The increases i n permeability induced by RMP-7 occurred in a dose-related fashion. No increase in carboplatin level was observed in several nonbrain tissue s, including sciatic nerve, retina, heart, lung, liver, kidney, and sp leen. Finally, the permeabilizing effects of RMP-7 were shown to occur independent of histaminergic or hypotensive mechanisms. These data pr ovide additional insight into the permeabilizing effects and mechanism of RMP-7 and offer additional support for the therapeutic utility of this novel compound as an adjunctive treatment for human gliomas.