Intracarotid infusion of bradykinin selectively increases blood-tumor permeability in 9L and C6 brain tumors.
This study investigated the effects of bradykinin on blood-tumor barrier (BTB) permeability in transplanted 9L gliosarcomas (9L) and C6 gliomas (C6) in rats. Permeability, expressed as the unidirectional transfer constant, Ki (microliter/g/min), was measured by quantitative autoradiography. Tracers used to examined permeability included radiolabeled alpha-aminoisobutyric acid ([14C]AIB), sucrose ([14C]sucrose) and dextran ([14C]dextran). Intracarotid infusion of bradykinin (10 mg/kg/min) significantly increased the BTB permeability in both 9L and C6 tumors to [14C]AIB and [14C]sucrose, but did not increase permeability to [14C]dextran. Blood-brain barrier (BBB) permeability in normal (non-tumor) brain was not significantly increased to any of the tracers by intracarotid bradykinin infusion. Ki values for [14C]AIB, [14C]sucrose and [14C]dextran of 9L tumors in the bradykinin group versus control group were 41.6 +/- 12.6 vs. 24.8 +/- 6.30 (P < 0.02), 17.5 +/- 9.34 vs. 9.05 +/- 4.36 (P < 0.05), and 3.90 +/- 2.59 vs. 2.42 +/- 1.76, respectively (mean +/- S.D.). Ki values to [14C]AIB, [14C]sucrose and [14C]dextran of C6 tumors in the bradykinin group versus control group were 41.4 +/- 19.0 vs. 19.5 +/- 11.4 (P < 0.01), 18.0 +/- 8.88 vs. 7.06 +/- 3.05 (P < 0.01), and 4.07 +/- 1.45 vs. 2.27 +/- 1.26, respectively (mean +/- S.D.). Intracarotid infusion of bradykinin did not significantly increase the blood volume in tumor or brain tissue despite its known vasodilative effect. Intracarotid infusion of bradykinin may be a useful technique for selective delivery of compounds to brain tumors.
Nomura
T
T
Brain Research Institute, Johnson Comprehensive Cancer Center, UCLA Medical Center 90024.
Inamura
T
T
Black
K L
KL
D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000818:Animals; D001345:Autoradiography; D001769:Blood / Q000378:metabolism*; D001920:Bradykinin / Q000008:administration & dosage* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism*; D002339:Carotid Arteries; D003911:Dextrans / Q000493:pharmacokinetics; D005260:Female; D005910:Glioma / Q000378:metabolism*; D018316:Gliosarcoma / Q000378:metabolism*; D007261:Infusions, Intra-Arterial; D010539:Permeability; D051381:Rats; D012016:Reference Values; D013395:Sucrose / Q000493:pharmacokinetics
D000621:Aminoisobutyric Acids; D003911:Dextrans; C100049:2-aminoisobutyric acid; D013395:Sucrose; D001920:Bradykinin