Article In-vivo Studies Radiobiology Year 1999

The combined effect of boronophenylalanine and borocaptate in boron neutron capture therapy for SCCVII tumors in mice

International Journal of Radiation Oncology Biology Physics, 1999

Authors:   Koji Ono,Shin Masunaga,Minoru Suzuki,Yuko Kinashi,Masao Takagaki,Mitsuhiko Akaboshi
Journal: International Journal of Radiation Oncology Biology Physics
Abstract: Purpose: To increase the effect of boron neutron capture therapy (BNCT) on tumors in vivo, the combined effects of para-boronophenylalanine (BPA) and borocaptate sodium (BSH) were investigated. Methods and Materials: 10B- enriched BPA and BSH were administered to C3H/He mice bearing SCCVII tumors by intragastric and intravenous injections, respectively. The colony formation and tumor control assays were employed for investigating antitumor effects of BNCT. The extent of homogeneity of tumor cell killing effect was examined by the distribution of frequencies of binuclear cells (BNC) producing a certain number of micronuclei (0,1,2,-,≥5) to total number of BNC and by the comparison between surviving cell fraction (SF) in colony division fraction formation assay and the normal nuclear (NNDF) at first mitosis following BNCT. Results: The relationships between SF and radiation dose in Gy (D) at around 10 ppm of 10B in tumors were as follow: – lnSF = – 0.101 + 0.648 Gy-1 x D, 0.0606 + 0.435 Gy-1 x D, and -0.0155 + 0.342 Gy-1 x D for BPA, BPA + BSH, and BSH, respectively. In tumor control assay, BPA was also more effective than BSH, but the difference of effectiveness significantly decreased: 1.9 times more effective in colony assay us. 1.2 times in tumor : Control assay. The most effective treatment to achieve tumor cure was BNCT using BPA + BSH, and it was 1.9 times more effective than BSH- BNCT. In BSH-BNCT, NNDF decreased exponentially with radiation dose and was equal to SF. However, NNDF following BPA-BNCT showed a bipbasic decrease with radiation dose, and SF was much lower than NNDF. In the combination of BPA and BSH, the discrepancy between NNDF and SF decreased in comparison with BPA-BNCT. The distribution of frequency of BNC with a certain number of micronuclei to total BNC was very close to Poisson distribution in BSH-BNCT tumors; however, it deviated from the Poisson in BPA-BNCT tumors. In combination with BPA and BSH, the distribution showed an intermediate pattern. These findings indicate that BSH distributes homogeneously with a heterogeneous distribution of BPA in tumors, and the heterogeneous effect of BPA-BNCT was improved by the combination of two boron compounds. Conclusion: The heterogeneous cell killing effect of BPA-BNCT was improved by the combination of BSH, and increased tumor control rates. Therefore, this combination may improve clinical outcome of BNCT although the effects on normal tissues have to be examined before clinical application.