Selective Opening of the Blood-Tumour Barrier by Intracarotid Infusion of Leukotriene C4
Intracarotid infusions of leukotriene C4 (LTC4) were used to selectively open the blood-tumour barrier in rats with RG-2 gliomas. Blood-brain and blood-tumour barrier permeability was determined by quantitative autoradiography using 14C aminoisobutyric acid. LTC4 (4 µg total dose) infused into the carotid artery ipsilateral to the tumour increased the unidirectional transfer constant for permeability, Ki, two-fold within the tumour while no effect on permeability was seen in the normal brain. No gamma glutamyl transpeptidase (γ-GTP) activity was seen in tumour capillaries in contrast to high γ-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 tumour capillaries. This could relate to the ability of γ-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-tumour barrier for delivery of antineoplastic compounds.
KeywordsSelective Opening Aminoisobutyric Acid Tumour Capillary Intracarotid Infusion Common Carotid Artery Bifurcation
- 4.Black KL, Betz AL, Ar DB (1987) Leukotriene C4 receptors in isolated brain capillaries. Adv Prostaglandin Thromboxane Leukotriene Res 17: 508–511Google Scholar