Abstract
Purpose
We evaluated the potential of a newly developed 10B-containing α-amino alcohol of p-boronophenylalanine-10B (BPA), p-boronophenylalaninol (BPAol), as a boron carrier in boron neutron capture therapy.
Methods
C57BL mice bearing EL4 tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously via implanted mini-osmotic pumps to label all proliferating (P) cells. After oral administration of L-BPA or D-BPA, or intraperitoneal injection of L-BPAol or D-BPAol, the tumors were irradiated with reactor thermal neutron beams. Some of the tumors were heated at 40 °C for 30 min (mild temperature hyperthermia (MTH)) right before neutron exposure, and/or tirapazamine (TPZ) was intraperitoneally injected 30 min before irradiation. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling [ =quiescent (Q) cells] was determined using immunofluorescence staining for BrdU. Meanwhile, 6 h after irradiation, tumor cell suspensions obtained in the same manner were used for determining the apoptosis frequency in Q cells. The apoptosis and MN frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU.
Results
Without TPZ or MTH, L- and D-BPAol increased both frequencies markedly, especially for total cells. Although not significantly larger, L-BPA and D-BPAol increased both frequencies slightly more than D-BPA and L-BPAol, respectively. Combination with both MTH and TPZ markedly reduced the sensitivity difference between total and Q cells.
Conclusion
Both L- and D-BPAol have potential as a 10B-carrier in neutron capture therapy, especially when combined with both MTH and TPZ.
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Acknowledgements
This study was supported, in part, by Grants-in-Aid for Scientific Research (B) (13470184) from the Japan Society for the Promotion of Science.
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Masunaga, Si., Ono, K., Kirihata, M. et al. Potential of α-amino alcohol p-boronophenylalaninol as a boron carrier in boron neutron capture therapy, regarding its enantiomers. J Cancer Res Clin Oncol 129, 21–28 (2003). https://doi.org/10.1007/s00432-002-0397-3
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DOI: https://doi.org/10.1007/s00432-002-0397-3