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


CONCLUSIONS
Both L- and D-BPAol have potential as a (10)B-carrier in neutron capture therapy, especially when combined with both MTH and TPZ.
Masunaga
Shin-Ichiro
S
Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University, Noda, Kumatori-cho, Sennan-gun, 590-0494, Osaka, Japan. smasuna@rri.kyoto-u.ac.jp
Ono
Koji
K
Kirihata
Mitsunori
M
Takagaki
Masao
M
Sakurai
Yoshinori
Y
Kinashi
Yuko
Y
Kobayashi
Tooru
T
Suzuki
Minoru
M
Nagata
Kenji
K
Nagasawa
Hideko
H
Uto
Yoshihiro
Y
Hori
Hitoshi
H
D000605:Amino Alcohols; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001880:Boranes; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004337:Drug Carriers; D005260:Female; D005455:Fluorescent Antibody Technique; D006979:Hyperthermia, Induced; D051379:Mice; D008810:Mice, Inbred C57BL; D010649:Phenylalanine / Q000031:analogs & derivatives*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology; D011879:Radiotherapy Dosage; D000077704:Tirapazamine; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology
D000605:Amino Alcohols; D001880:Boranes; D004337:Drug Carriers; D011838:Radiation-Sensitizing Agents; D014227:Triazines; C447034:boronophenylalaninol; D000077704:Tirapazamine; D010649:Phenylalanine