Pharmacokinetic study of BSH and BPA in simultaneous use for BNCT.
In order to improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, we examined the optimization of the administration of boron compounds in brain tumor animal model. We analyzed the concentration of boron atoms in intracranial C6 glioma -bearing rats using inductively coupled plasma atomic emission spectrometry. Each tumor-bearing rat received one of two different amounts of sodium borocaptate (BSH) and/or 500 mg/kg of boronophenylalanine (BPA) via intraperitoneal injection. We compared the boron concentrations of the tumor, the contralateral normal brain and the blood in rats of 3 different treatment groups (BSH alone, BPA alone and a combination of both BSH and BPA). Our results show that the tumor boron concentration increased much more than 30 microg/g by the coadministration of both compounds. Additionally, the blood boron concentration remained below 30 microg/g and the boron concentration in the normal brain was low (mean 4.7+/-1.1 microg/g). Even in comparison with the administration of BPA alone, coadministration of BPA and BSH shows an improved tumor/normal brain ratio of boron concentrations.
Department of Neurosurgery, Osaka Medical College, Takatsuki Osaka, Japan.
Kunio
K
Yokoyama
Shin-Ichi
S
Miyatake
Yoshinaga
Y
Kajimoto
Shinji
S
Kawabata
Atsushi
A
Doi
Toshiko
T
Yoshida
Tomoyuki
T
Asano
Mitsunori
M
Kirihata
Koji
K
Ono
Toshihiko
T
Kuroiwa
D000818:Animals; D001894:Borohydrides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001896:Boron Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D004338:Drug Combinations; D004357:Drug Synergism; D005910:Glioma / Q000378:metabolism* / Q000532:radiotherapy; D008297:Male; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011879:Radiotherapy Dosage; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
C436045:4-dihydroxyborylphenylalanine; D001894:Borohydrides; D001896:Boron Compounds; D004338:Drug Combinations; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D010649:Phenylalanine