Enhanced tumor uptake of carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7

Neurosurgery. 1996 Jul;39(1):125-33; discussion 133-4. doi: 10.1097/00006123-199607000-00025.


Objective: Intracarotid infusion of the bradykinin analog, RMP-7, can increase permeability in brain tumor capillaries. This study sought to determine the following: 1) the unidirectional transport, Ki, of radiolabeled [14C]carboplatin into brain tumors with either intravenous or intracarotid RMP-7 infusions; 2) the duration and extent of increased permeability in tumor capillaries during continuous RMP-7 infusions; and 3) the effect on survival of carboplatin combined with RMP-7 treatment in rats with gliomas.

Methods: Wistar rats with RG2 gliomas were used, and a unidirectional transfer constant, Ki, was determined using quantitative autoradiography. In the survival study, the rats were treated with intra-arterial carboplatin and RMP-7 at Days 5 and 7 after tumor implantation.

Results: Intracarotid infusion of RMP-7 for 15 minutes increased the transport of [14C]carboplatin to tumors by 2.7-fold, as compared with saline infusion alone (P < 0.001). The transports of [14C]dextran and [14C]carboplatin into tumors were significantly higher with 15 minutes of intracarotid infusion of RMP-7 (0.1 microgram/kg/min), compared to those with 10-, 30-, or 60-minute infusions (P < 0.01). Rats treated at Days 5 and 7 after tumor implantation with carboplatin alone (10 mg/kg) exhibited a modest increase in survival at 31 days (37%, compared to < 10% of controls), while those given the combination of carboplatin with RMP-7 exhibited a significantly higher survival rate (74%).

Conclusion: Intracarotid infusion of RMP-7 can selectively increase transport of carboplatin into brain tumors and results in higher survival in rats with gliomas. These findings support the use of intracarotid infusion of RMP-7 to enhance the delivery of carboplatin to patients with malignant brain tumors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Autoradiography
  • Blood-Brain Barrier / drug effects*
  • Bradykinin / analogs & derivatives*
  • Bradykinin / pharmacology
  • Brain / blood supply
  • Brain / pathology
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Capillary Permeability / drug effects
  • Carboplatin / administration & dosage
  • Carboplatin / pharmacokinetics*
  • Carotid Arteries
  • Dose-Response Relationship, Drug
  • Female
  • Glioma / blood supply
  • Glioma / drug therapy*
  • Glioma / pathology
  • Infusions, Intra-Arterial
  • Infusions, Intravenous
  • Rats
  • Rats, Wistar
  • Survival Rate


  • Antineoplastic Agents
  • RMP 7
  • Carboplatin
  • Bradykinin