ENHANCED DELIVERY OF BORONOPHENYLALANINE FOR NEUTRON-CAPTURE THERAPY BY MEANS OF INTRACAROTID INJECTION AND BLOOD-BRAIN-BARRIER DISRUPTION

THERE HAS BEEN increasing interest in the possible use of boronophenyl alanine as a capture agent for boron neutron capture therapy of brain tumors. The purpose of the present study was to determine whether the uptake of boronophenylalanine in F98 glioma-bearing rats could be enha nced by means of intracarotid (i.c.) injection with or without blood-b rain barrier disruption (BBB-D). Glioma cells (10(5)) were stereotacti cally implanted into the right cerebral hemisphere of Fischer rats, an d 12 days later, BBB-D was performed by infusing 25% mannitol (1.373 m Osmol/ml) into the right carotid artery and then immediately injecting L-boronophenylalanine (300 mg/kg of body weight) intracarotidly. The animals were killed 0.5, 1, 2.5, and 4 hours later, and the brains wer e removed for boron determination by direct current plasma atomic emis sion spectroscopy. BBB-D was assessed by the intravenous injection of Evans blue or horseradish peroxidase, and the barrier-disrupted hemisp heres and tumors showed intense staining with each. The mean tumor bor on concentration after i.c. injection and BBB-D was 34.8 +/- 6.8 mu g/ g at 2.5 hours compared with 20.3 +/- 6.2 mu g/g after i.c. injection without BBB-D and 10.7 +/- 0.7 mu g/g after intravenous injection. No significant differences in boron concentration in muscle, skin, and ey e were observed among the different groups. Boron concentrations in th e ipsilateral, disrupted hemisphere increased transiently but rapidly returned to background levels by 2.5 hours after BBB-D. The tumor:brai n and tumor:blood ratios were 5.2 and 5.6, respectively, compared to 3 .2 and 2.1 for intravenous injection groups at 2.5 hours. The present study is the first to show that BBB-D combined with i.c. injection can enhance the tumor uptake of boron compounds for boron neutron capture therapy.