Tissue uptake of BSH in patients with glioblastoma in the EORTC 11961 phase I BNCT trial.
OBJECTIVE
The uptake of the boron compound Na2B12H10-SH (BSH) in tumor and normal tissues was investigated in the frame of the EORTC phase I trial 'Postoperative treatment of glioblastoma with BNCT at the Petten Irradiation Facility' (protocol 11961).


METHODS
The boron concentration in blood, tumor, normal brain, dura, muscle, skin and bone was detected using inductively coupled plasma-atomic emission spectroscopy in 13 evaluable patients. In a first group of 10 patients 100 mg BSH/kg bodyweight (BW) were administered; a second group of 3 patients received 22.9 mg BSH/kg BW. The toxicity due to BSH was evaluated.


RESULTS
The average boron concentration in the tumor was 19.9 +/- 9.1 ppm (1 standard deviation (SD)) in the high dose group and 9.8 +/- 3.3 ppm in the low dose group, the tumor/blood ratios were 0.6 +/- 0.2 and 0.9 +/- 0.2, respectively. The highest boron uptake has been detected in the dura, very low uptake was found in the bone, the cerebro-spinal fluid and especially in the brain (brain/blood ratio 0.2 +/- 0.02 and 0.4 +/- 0.2). No toxicity was detected except flush-like symptoms in 2 cases during a BSH infusion at a much higher speed than prescribed.


CONCLUSIONS
BSH proved to be safe for clinical application at a dose of 100 mg BSH/kg infused and at a dose rate of 1 mg/kg/min. The study underlines the importance of a further investigation of BSH uptake in order to obtain enough data for significant statistical analysis. The boron concentration in blood seems to be a quite reliable parameter to predict the boron concentration in other tissues.
Department of Radiotherapy, University Essen, Germany.
Katalin
K
Hideghéty
Wolfgang
W
Sauerwein
Andrea
A
Wittig
Claudia
C
Götz
Philippe
P
Paquis
Frank
F
Grochulla
Klaus
K
Haselsberger
John
J
Wolbers
Ray
R
Moss
Rene
R
Huiskamp
Heinz
H
Fankhauser
Martin
M
de Vries
Detlef
D
Gabel
D000368:Aged; D001895:Boron / Q000009:adverse effects / Q000032:analysis* / Q000493:pharmacokinetics*; D001896:Boron Compounds / Q000008:administration & dosage / Q000009:adverse effects; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects; D001932:Brain Neoplasms / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D014018:Tissue Distribution
D001896:Boron Compounds; D001895:Boron