title: Increased delivery of a new cisplatin analogue (254-S) in a rat brain tumor by an intracarotid infusion of bradykinin.
abstract: The intracarotid infusion of bradykinin has been shown to selectively increase capillary permeability in a brain tumor without affecting either normal brain capillary permeability or the systemic blood pressure. We examined whether the intracarotid infusion of bradykinin could selectively increase the delivery of a new watersoluble antitumor agent, cis-diammine glycolato-platinum (254-S, 303.2 mol. wt.), to transplanted RG2 glioma in rats. The platinum contents in the brain, tumor tissues and plasma were measured using an atomic absorption spectrophotometer. The transfer ratio of 254-S from plasma to the tissues was calculated and expressed as the volume of plasma containing platinum per g tissue (Dp, microliter g-1). Intracarotid bradykinin infusion at a rate of 20 micrograms kg-1 min-1 increased the delivery of 254-S in the tumor tissue by 1.3-fold when compared with intracarotid infusion of 0.9% saline (48.78 +/- 18.11 vs. 37.12 +/- 12.53; p < 0.05). In normal brain tissue including the ipsilateral cortex, the contralateral basal ganglia and the contralateral cortex, bradykinin did not significantly increase the delivery of 254-S in comparison with 0.9% saline (12.28 +/- 9.53 vs. 10.70 +/- 5.05, 4.96 +/- 3.54 vs 4.96 +/- 4.80, 7.64 +/- 4.10 vs. 13.07 +/- 11.38, respectively). These results indicate that the intracarotid infusion of bradykinin selectively increases the delivery of 254-S to the brain tumor without affecting the normal brain. This method may, therefore, enhance the antitumor effect of 254-S for the treatment of brain tumors and also reduce neurotoxicity in the normal brain.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Koga
authors.forename: T
authors.initials: T
authors.lastname: Inamura
authors.forename: K
authors.initials: K
authors.lastname: Ikezaki
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Samoto
authors.forename: M
authors.initials: M
authors.lastname: Fukui
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000031:analogs & derivatives*; D005910:Glioma / Q000188:drug therapy*; D008297:Male; D009944:Organoplatinum Compounds / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C053989:nedaplatin; D002945:Cisplatin; D001920:Bradykinin