Subcellular biodistribution of sodium borocaptate (BSH: Na2B12H11SH) in a rat glioma model in boron neutron capture therapy.
Mercaptoundecahydrododecaborate (Na2B12H111SH, sodium borocaptate or 'BSH') has been used clinically as a boron compound for boron neutron capture therapy (BNCT) in patients with malignant glioma in Japan and Europe. Boron-10 is known to accumulate selectively only in brain tumor cells. This work was aimed to clarify the subcellular biodistribution of BSH in a rat glioma model using immunohistochemical approach. Wistar rats were used for this experiment. An intracerebral injection of 5.0 x 10(6) C6 glioma cells was introduced into the region of cerebral hemisphere. Fifty milligrams of "'B/kg BSH was infused intravenously two weeks after implantation. Host rats were divided into six groups according to the sampling time: 1, 4, 8, 16, 24 and 48 h after the start of BSH infusion. Immunohistochemical study was carried out using anti-BSH antibody. Boron was already found in a whole cell 1 h after BSH infusion, and then seemed to collect in a cell nuclei around 8-16 h after infusion. It was still recognized in tumor cell 48 h after infusion. This study supports the following hypothesis on selective boron uptake in a tumor. BSH can pass through the disrupted blood-brain barrier (BBB) easily and can come in contact with tumor cells; there, BSH can bind on the extracellular surface of plasma membrane to choline residues. After binding to the plasma membrane, boron with choline residues may be internalized into the cell by endocytic pathways and eventually travel to cell nuclei, and then stay there for a long time.
Kageji
Teruyoshi
T
Department of Neurological Surgery, School of Medicine, The University of Tokushima, Japan. kageji@clin.med.tokushima-u.ac.jp
Nagahiro
Shinji
S
Otersen
Birte
B
Gabel
Detlef
D
Nakaichi
Manekazu
M
Nakagawa
Yoshinobu
Y
D000818:Animals; D001894:Borohydrides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001895:Boron / Q000032:analysis; D016754:Boron Neutron Capture Therapy / Q000379:methods; D001932:Brain Neoplasms / Q000737:chemistry / Q000378:metabolism*; D005910:Glioma / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution
D001894:Borohydrides; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D001895:Boron