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 micrograms 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 (gamma-GTP) activity was seen in tumour 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 tumour 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-tumour barrier for delivery of antineoplastic compounds.
Black
K L
KL
Brain Research Institute, Jonsson Cancer Center, Los Angeles, California.
King
W A
WA
Ikezaki
K
K
D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply*; D002196:Capillaries / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D002339:Carotid Arteries; D005260:Female; D005910:Glioma / Q000098:blood supply*; D007269:Injections, Intra-Arterial; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D013189:SRS-A / Q000008:administration & dosage* / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D013189:SRS-A; D005723:gamma-Glutamyltransferase