Intracarotid infusion of RMP-7, a bradykinin analog: a method for selective drug delivery to brain tumors

Abstract

✓ The bradykinin analog, RMP-7, was investigated for its ability to selectively increase uptake of molecular tracers in RG2 glial tumors. When infused in low doses (0.1 µg/kg/min) through the intracarotid artery ipsilateral to RG2 gliomas in rats, RMP-7 significantly increased the permeability of tumor capillaries to methotrexate and to four other tracers of varying molecular weights, compared to intracarotid infusion of vehicle alone. Tracers used to examine permeability included radiolabeled α-aminoisobutyric acid (Mr 103 D), sucrose (Mr 342 D), methotrexate (Mr 454.5 D), inulin (Mr 5000 D), and dextran (Mr 70,000 D). Permeability was expressed as the unidirectional transfer constant, Ki (µl/gm/min). The permeability (Ki) of tumors in the RMP-7 group compared to the vehicle control group was as follows: α-aminoisobutyric acid, 35.3 ± 9.11 versus 12.7 ± 4.56 (p < 0.001); sucrose, 16.5 ± 3.83 versus 9.28 ± 3.12 (p < 0.05); methotrexate, 26.3 ± 10.3 versus 8.98 ± 6.78 (p < 0.005); inulin, 13.5 ± 3.23 versu...