Optimal timing of neutron irradiation for boron neutron capture therapy after intravenous infusion of sodium borocaptate in patients with glioblastoma.
OBJECTIVE
A cooperative study in Europe and Japan was conducted to determine the pharmacokinetics and boron uptake of sodium borocaptate (BSH: Na(2)B(12)H(11)SH), which has been introduced clinically as a boron carrier for boron neutron capture therapy in patients with glioblastoma.


METHODS
Data from 56 patients with glioblastoma who received BSH intravenous infusion were retrospectively reviewed. The pharmacokinetics were evaluated in 50 patients, and boron uptake was investigated in 47 patients. Patients received BSH doses between 12 and 100 mg/kg of body weight. For the evaluation, the infused boron dose was scaled linearly to 100 mg/kg BSH.


RESULTS
In BSH pharmacokinetics, the average value for total body clearance, distribution volume of steady state, and mean residence time was 3.6 +/- 1.5 L/h, 223.3 +/- 160.7 L, and 68.0 +/- 52.5 h, respectively. The average values of the boron concentration in tumor adjusted to 100 mg/kg BSH, the boron concentration in blood adjusted to 100 mg/kg BSH, and the tumor/blood boron concentration ratio were 37.1 +/- 35.8 ppm, 35.2 +/- 41.8 ppm, and 1.53 +/- 1.43, respectively. A good correlation was found between the logarithmic value of T(adj) and the interval from BSH infusion to tumor tissue sampling. About 12-19 h after infusion, the actual values for T(adj) and tumor/blood boron concentration ratio were 46.2 +/- 36.0 ppm and 1.70 +/- 1.06, respectively. The dose ratio between tumor and healthy tissue peaked in the same interval.


CONCLUSIONS
For boron neutron capture therapy using BSH administered by intravenous infusion, this work confirms that neutron irradiation is optimal around 12-19 h after the infusion is started.
Kageji
T
T
Department of Neurological Surgery, University of Tokushima School of Medicine, Tokushima, Japan. Kageji@clin.med.tokushima-u.ac.jp
Nagahiro
S
S
Kitamura
K
K
Nakagawa
Y
Y
Hatanaka
H
H
Haritz
D
D
Grochulla
F
F
Haselsberger
K
K
Gabel
D
D
D000328:Adult; D000368:Aged; D001894:Borohydrides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D002648:Child; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013997:Time Factors
D001894:Borohydrides; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate