Improved survival after boron neutron capture therapy of brain tumors by Cereport-mediated blood-brain barrier modulation to enhance delivery of boronophenylalanine.

摘要: OBJECTIVE Cereport (Alkermes, Inc., Cambridge, MA), or, as it has been previously called, RMP-7 (receptor-mediated permeabilizer-7), is a bradykinin analog that shown to produce transient, pharmacologically mediated opening of the blood-brain barrier. The purpose present study was determine whether efficacy boron neutron capture therapy (BNCT) could be enhanced by means intracarotid (i.c.) infusion Cereport, in combination with intravenous (i.v.) injection or i.c. boronophenylalanine (BPA) F98 rat glioma model. METHODS For biodistribution studies, Fischer rats bearing intracerebral implants received i.v. injections 300 500 mg/kg body weight (b.w.) BPA without 1.5 microg/kg b.w. Cereport. BNCT initiated 14 days after implantation 10(3) cells. (500 b.w.) given and animals were irradiated 2.5 hours later at Brookhaven Medical Research Reactor collimated beam thermal neutrons delivered head. RESULTS At dose b.w., tumor concentrations (mean +/- standard deviation) 55.7 9.6 microg/g versus 33.6 3.9 BPA, 29.4 9.9 15.4 3.5 (P < 0.05) BPA. After administration tumor-to-blood ratio 5.4 0.6, tumor-to-brain 5.2 2.4. mg/kg, survival time 50 16 for 40 6 = 0.05), 38 4 34 3 0.02), 28 5 controls, 23 untreated controls. Compared there 117% increase lifespan an then 86% CONCLUSION These studies have established can not only uptake but also enhance BNCT.