Abstract
INTRODUCTION
Boron neutron capture therapy (BNCT) is form of tumor-cell selective particle irradiation. Although novel boron compounds have been developed, BPA (boronophenylalanine) and BSH (borocaptate sodium) are used in the clinical practice. The development of effective boron compounds is a major theme. We used Dodecaborate-containing BPA (AAL) which is combined the characteristics of both BPA and BSH. We have been conducting research on how the new compound for BNCT will affect rat brain tumor model.
MATERIALS AND METHODS
We evaluated the boron concentration of F98 glioma cells for BPA and AAL, and the biodistribution of these following BPA administrated intravenously (i.v.) or AAL administrated by convection-enhanced delivery (CED) in F98 glioma bearing rats. In BNCT study, the therapeutic effect was evaluated in terms of the survival time for all rats divided into six groups.
RESULTS
The uptake of boron showed almost the same value at all exposure times in high concentration. In biodistribution study, the AAL(CED) 6h after the termination group attained the highest boron concentrations of the tumor (59.9 ± 18.2 μg/g). In the BNCT study, the median survival time in the AAL(CED) group (31(29–35) days) was shorter than that in the BPA(i.v.) group(34(33–36) days). And the combination group of AAL(CED) and BPA(i.v.) gave the most significant prolongation of survival(38(36–40) days).
DISCUSSION
AAL(CED) and BPA(i.v.) combined group had a significant survival prolongation compared with the single-agent group. It is thought that AAL irradiated by thermal neutron had a cell-killing effect on cells in which BPA was not taken up. The combination uses of AAL (CED) provides additional BNCT effects. The mechanism by which AAL is incorporated has not been clarified, and further experiments including the influence on normal cells are in progress.
CONCLUSION
Dodecaborate-containing BPA (AAL) is a novel boron compound for BNCT that can be expected to prolong the survival time in combination with BPA.