The combined effect of electroporation and borocaptate in boron neutron capture therapy for murine solid tumors.
10 B-Enriched borocaptate (BSH) was administered intraperitoneally to SCCVII tumor-bearing C3H / He mice. Electroporation (EP) was conducted by using a tweezers-type electrode. The (10) B contents in tumors were measured by prompt gamma-ray spectrometry. The colony formation assay was applied to investigate the antitumor effects of boron neutron capture therapy (BNCT) and thereby to estimate the intratumor localization of BSH. The (10) B concentrations in tumors decreased with time following BSH administration, falling to 5.4(0. 1) ppm at 3 h, whereas EP treatment (3 repetitions) 15 min after BSH injection delayed the clearance of BSH from tumors, and the (10) B level remained at 19.4(0.9) ppm at 3 h. The effect of BNCT increased with the (10) B concentration in tumors, and the combination with EP showed a remarkably large cell killing effect even at 3 h after BSH injection. The effect of BNCT, i.e., slope coefficient of the cell survival curve of tumors, without EP was proportional to tumor (10) B level (r = 0.982), and that of BSH-BNCT combined with EP lay close to the same correlation line. However, tumors subjected to EP after BSH injection did not show high radiosensitivity when irradiated after conversion to a single cell suspension by enzymatic digestion. This indicates that the increase of the BNCT effect by EP was a consequence of enclosure of BSH in the interstitial space of tumor tissue and not within tumor cells. This is different from a previous in vitro study. The combination of EP and BNCT may be clinically useful, if a procedure to limit EP to the tumor region becomes available or if an alternative similar method is employed.
Ono
K
K
Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka 590-0494, Japan. onokoji@rri.kyoto-u.ac.jp
Kinashi
Y
Y
Suzuki
M
M
Takagaki
M
M
Masunaga
S I
SI
D000818:Animals; D001894:Borohydrides / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy; D004195:Disease Models, Animal; D018274:Electroporation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000532:radiotherapy*; D013438:Sulfhydryl Compounds / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D001894:Borohydrides; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate