Selective opening of the blood-tumor barrier by intracarotid infusion of leukotriene C4

Abstract

Intracarotid infusions of leukotriene C4 (LTC4) were used to selectively open the blood-tumor barrier in rats with RG-2 gliomas. Blood-brain and blood-tumor permeability was determined by quantitative autoradiography using 14C aminoisobutyric acid. Leukotriene C4 (4 micrograms total dose) infused into the carotid artery ipsilateral to the tumor increased twofold the unidirectional transfer constant for permeability within the tumor while no effect on permeability was seen in normal brain. No gamma glutamyl transpeptidase (gamma-GTP) activity was seen in tumor capillaries in contrast to high gamma-GTP in normal brain capillaries. These findings suggest that normal brain capillaries may resist the vasogenic effects of LTC4, while LTC4 will increase permeability in tumor capillaries. This could relate to the ability of gamma-GTP to act as an enzymatic barrier and inactivate leukotrienes in normal brain capillaries. Intracarotid LTC4 infusion may be a useful tool to selectively open the blood-tumor barrier for delivery of antineoplastic compounds.