title: Effects of employing a ¹⁰B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy.
abstract: OBJECTIVE
  To evaluate the effects of employing a (10)B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells.
  
  
  METHODS
  B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a (10)B-carrier [L-para-boronophenylalanine-(10)B (BPA) or sodium mercaptoundecahydrododecaborate-(10)B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation.
  
  
  RESULTS
  BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a (10)B-carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT.
  
  
  CONCLUSIONS
  BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases.
authors.affiliation: Particle Radiation Oncology Research Centre, Research Reactor Institute, Kyoto University, Osaka, Japan. smasuna@rri.kyoto-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Masunaga
authors.forename: Y
authors.initials: Y
authors.lastname: Sakurai
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: N
authors.initials: N
authors.lastname: Kondo
authors.forename: A
authors.initials: A
authors.lastname: Maruhashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kinashi
authors.forename: K
authors.initials: K
authors.lastname: Ono
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001894:Borohydrides / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001973:Bromodeoxyuridine; D015687:Cell Hypoxia / Q000187:drug effects; D005260:Female; D006979:Hyperthermia, Induced / Q000379:methods*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009536:Niacinamide / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012878:Skin Neoplasms / Q000532:radiotherapy*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001894:Borohydrides; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; D014803:Vitamin B Complex; C014651:mercaptoundecahydrododecaborate; D009536:Niacinamide; D001973:Bromodeoxyuridine