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Evaluation of the Potential of p‐Boronophenylalaninol as a Boron Carrier in Boron Neutron Capture Therapy, Referring to the Effect on Intratumor Quiescent Cells

C57BL mice bearing EL4 tumors and C3H/He mice bearing SCC VII tumors received 5‐bromo‐2′‐deoxyuridine (BrdU) continuously for 5 days via implanted mini‐osmotic pumps to label all proliferating (P) cells. Three hours after oral administration of l‐p‐boronophenylalanine‐(10)B (BPA), or 30 min after in...

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Autores principales: Masunaga, Shin‐ichiro, Ono, Koji, Kirihata, Mitsunori, Takagaki, Masao, Sakurai, Yoshinori, Kinashi, Yuko, Kobayashi, Tooru, Nagasawa, Hideko, Uto, Yoshihiro, Hori, Hitoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926838/
https://www.ncbi.nlm.nih.gov/pubmed/11572769
http://dx.doi.org/10.1111/j.1349-7006.2001.tb01191.x
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author Masunaga, Shin‐ichiro
Ono, Koji
Kirihata, Mitsunori
Takagaki, Masao
Sakurai, Yoshinori
Kinashi, Yuko
Kobayashi, Tooru
Nagasawa, Hideko
Uto, Yoshihiro
Hori, Hitoshi
author_facet Masunaga, Shin‐ichiro
Ono, Koji
Kirihata, Mitsunori
Takagaki, Masao
Sakurai, Yoshinori
Kinashi, Yuko
Kobayashi, Tooru
Nagasawa, Hideko
Uto, Yoshihiro
Hori, Hitoshi
author_sort Masunaga, Shin‐ichiro
collection PubMed
description C57BL mice bearing EL4 tumors and C3H/He mice bearing SCC VII tumors received 5‐bromo‐2′‐deoxyuridine (BrdU) continuously for 5 days via implanted mini‐osmotic pumps to label all proliferating (P) cells. Three hours after oral administration of l‐p‐boronophenylalanine‐(10)B (BPA), or 30 min after intraperitoneal injection of sodium borocaptate‐(10)B (BSH) or l‐p‐boronophenylalaninol (BPA‐ol), a newly developed (10)B‐containing α‐amino alcohol, the tumors were irradiated with thermal neutron beams. For the combination with mild temperature hyperthermia (MTH) and/or tirapazamine (TPZ), the tumors were heated at 40°C for 30 min immediately before neutron exposure, and 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 MN and apoptosis frequency in total (P+Q) tumor cells were determined from tumors that were not pretreated with BrdU. Without TPZ or MTH, BPA‐ol increased both frequencies most markedly, especially for total cells. However, as with BPA, the sensitivity difference between total and Q cells was much larger than with BSH. On combined treatment with both MTH and TPZ, this sensitivity difference was markedly reduced, similarly to when BPA was used. MTH increased the (10)B uptake of all (10)B‐compounds into both tumor cells. BPA‐ol has good potential as a (10)B‐carrier in neutron capture therapy, especially when combined with both MTH and TPZ.
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spelling pubmed-59268382018-05-11 Evaluation of the Potential of p‐Boronophenylalaninol as a Boron Carrier in Boron Neutron Capture Therapy, Referring to the Effect on Intratumor Quiescent Cells Masunaga, Shin‐ichiro Ono, Koji Kirihata, Mitsunori Takagaki, Masao Sakurai, Yoshinori Kinashi, Yuko Kobayashi, Tooru Nagasawa, Hideko Uto, Yoshihiro Hori, Hitoshi Jpn J Cancer Res Article C57BL mice bearing EL4 tumors and C3H/He mice bearing SCC VII tumors received 5‐bromo‐2′‐deoxyuridine (BrdU) continuously for 5 days via implanted mini‐osmotic pumps to label all proliferating (P) cells. Three hours after oral administration of l‐p‐boronophenylalanine‐(10)B (BPA), or 30 min after intraperitoneal injection of sodium borocaptate‐(10)B (BSH) or l‐p‐boronophenylalaninol (BPA‐ol), a newly developed (10)B‐containing α‐amino alcohol, the tumors were irradiated with thermal neutron beams. For the combination with mild temperature hyperthermia (MTH) and/or tirapazamine (TPZ), the tumors were heated at 40°C for 30 min immediately before neutron exposure, and 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 MN and apoptosis frequency in total (P+Q) tumor cells were determined from tumors that were not pretreated with BrdU. Without TPZ or MTH, BPA‐ol increased both frequencies most markedly, especially for total cells. However, as with BPA, the sensitivity difference between total and Q cells was much larger than with BSH. On combined treatment with both MTH and TPZ, this sensitivity difference was markedly reduced, similarly to when BPA was used. MTH increased the (10)B uptake of all (10)B‐compounds into both tumor cells. BPA‐ol has good potential as a (10)B‐carrier in neutron capture therapy, especially when combined with both MTH and TPZ. Blackwell Publishing Ltd 2001-09 /pmc/articles/PMC5926838/ /pubmed/11572769 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01191.x Text en
spellingShingle Article
Masunaga, Shin‐ichiro
Ono, Koji
Kirihata, Mitsunori
Takagaki, Masao
Sakurai, Yoshinori
Kinashi, Yuko
Kobayashi, Tooru
Nagasawa, Hideko
Uto, Yoshihiro
Hori, Hitoshi
Evaluation of the Potential of p‐Boronophenylalaninol as a Boron Carrier in Boron Neutron Capture Therapy, Referring to the Effect on Intratumor Quiescent Cells
title Evaluation of the Potential of p‐Boronophenylalaninol as a Boron Carrier in Boron Neutron Capture Therapy, Referring to the Effect on Intratumor Quiescent Cells
title_full Evaluation of the Potential of p‐Boronophenylalaninol as a Boron Carrier in Boron Neutron Capture Therapy, Referring to the Effect on Intratumor Quiescent Cells
title_fullStr Evaluation of the Potential of p‐Boronophenylalaninol as a Boron Carrier in Boron Neutron Capture Therapy, Referring to the Effect on Intratumor Quiescent Cells
title_full_unstemmed Evaluation of the Potential of p‐Boronophenylalaninol as a Boron Carrier in Boron Neutron Capture Therapy, Referring to the Effect on Intratumor Quiescent Cells
title_short Evaluation of the Potential of p‐Boronophenylalaninol as a Boron Carrier in Boron Neutron Capture Therapy, Referring to the Effect on Intratumor Quiescent Cells
title_sort evaluation of the potential of p‐boronophenylalaninol as a boron carrier in boron neutron capture therapy, referring to the effect on intratumor quiescent cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926838/
https://www.ncbi.nlm.nih.gov/pubmed/11572769
http://dx.doi.org/10.1111/j.1349-7006.2001.tb01191.x
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