Intravenous RMP-7 selectively increases uptake of carboplatin into rat brain tumors

• Published in: Cancer research (Chicago, Ill.) Vol. 56; no. 17; pp. 3998 - 4005
• Main Authors: ELLIOTT, P. J, HAYWARD, N. J, DEAN, R. L, BLUNT, D, BARTUS, R. T
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-09-1996
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - toxicity; Autoradiography; Biological and medical sciences; Blood-Brain Barrier; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Brain - metabolism; Brain Neoplasms - metabolism; Capillary Permeability; Carbon Radioisotopes; Carboplatin - pharmacokinetics; Carboplatin - pharmacology; Chemotherapy; Dose-Response Relationship, Drug; Drug Interactions; Female; Glioma - metabolism; Histamine - physiology; Hypotension - physiopathology; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Wistar; Antineoplastic agent; Intracranial; Nervous system diseases; Drug combination; Intravenous administration; Rat; Rodentia; Permeability; Malignant tumor; Blood brain barrier; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Glioma; Animal; Central nervous system disease; Drug interaction; Mechanism of action; Platinum II Complexes
• ISSN: 0008-5472; 1538-7445

Rats implanted with RG-2 gliomas were administered i.v. RMP-7 and [14C]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 vascular barrier within the tumor to carboplatin. Additionally, permeability of brain tissue proximal to, but clearly outside the tumor mass, was also increased. Progressively less uptake of [14C]carboplatin was observed as distance from the tumor border increased. The increases in permeability induced by RMP-7 occurred in a dose-related fashion. No increase in carboplatin level was observed in several nonbrain tissues, including sciatic nerve, retina, heart, lung, liver, kidney, and spleen. Finally, the permeabilizing effects of RMP-7 were shown to occur independent of histaminergic or hypotensive mechanisms. These data provide 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.