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, K-i (mu l/g/min), was measured by quantitative autoradiography. Tracers used to examined permeability included radiolabeled alpha-aminoisobutyric acid ([C-14]AIB), sucrose ([C-14]sucrose) and dextran ([C-14]dextran). Intracarotid infusion of bradykinin (10 mg/kg/min) significantly increased the BTB permeability in both 9L and C6 tumors to [C-14]AIB and [C-14]sucrose, but did not increase permeability to [C-14]dextran. Blood-brain barrier (BBB) permeability in normal (non-tumor) brain was not significantly increased to any of the tracers by intracarotid bradykinin infusion. K-i values for [C-14]AIB, [C-14]sucrose and [C-14]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.). K-i values to [C-14]AIB, [C-14]sucrose and [C-14]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 bt: a useful technique for selective delivery of compounds to brain tumors.