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  • Title: Potential of alpha-amino alcohol p-boronophenylalaninol as a boron carrier in boron neutron capture therapy, regarding its enantiomers.
    Author: Masunaga S, Ono K, Kirihata M, Takagaki M, Sakurai Y, Kinashi Y, Kobayashi T, Suzuki M, Nagata K, Nagasawa H, Uto Y, Hori H.
    Journal: J Cancer Res Clin Oncol; 2003 Jan; 129(1):21-8. PubMed ID: 12618897.
    Abstract:
    PURPOSE: We evaluated the potential of a newly developed (10)B-containing alpha-amino alcohol of p-boronophenylalanine-(10)B (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 degrees 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 (10)B-carrier in neutron capture therapy, especially when combined with both MTH and TPZ.
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