Potential of alpha-amino alcohol p-boronophenylalaninol as a boron carrier in boron neutron capture therapy, regarding its enantiomers

J Cancer Res Clin Oncol. 2003 Jan;129(1):21-8. doi: 10.1007/s00432-002-0397-3. Epub 2003 Jan 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Alcohols*
  • Animals
  • Apoptosis / radiation effects
  • Boranes*
  • Boron Neutron Capture Therapy / methods*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Carriers
  • Female
  • Fluorescent Antibody Technique
  • Hyperthermia, Induced
  • Mice
  • Mice, Inbred C57BL
  • Phenylalanine* / analogs & derivatives*
  • Radiation-Sensitizing Agents / administration & dosage
  • Radiation-Sensitizing Agents / pharmacology
  • Radiotherapy Dosage
  • Tirapazamine
  • Triazines / administration & dosage
  • Triazines / pharmacology


  • Amino Alcohols
  • Boranes
  • Drug Carriers
  • Radiation-Sensitizing Agents
  • Triazines
  • boronophenylalaninol
  • Tirapazamine
  • Phenylalanine