title: The dependency of compound biological effectiveness factors on the type and the concentration of administered neutron capture agents in boron neutron capture therapy.
abstract: OBJECTIVE
  To examine the effect of the type and the concentration of neutron capture agents on the values of compound biological effectiveness (CBE) in boron neutron capture therapy.
  
  
  METHODS
  After the subcutaneous administration of a (10) B-carrier, boronophenylalanine- (10) B (BPA) or sodium mercaptododecaborate- (10) B (BSH), at 3 separate concentrations, the (10) B concentrations in tumors were measured by γ-ray spectrometry. SCC VII tumor-bearing C3H/He mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells, then treated with BPA or BSH. Immediately after reactor neutron beam irradiation, during which intratumor (10) B concentrations were kept at levels similar to each other, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of BrdU-unlabeled quiescent (Q) and total (= P + Q) tumor cells were assessed based on the frequencies of micronucleation using immunofluorescence staining for BrdU.
  
  
  RESULTS
  The CBE values were higher in Q cells and in the use of BPA than total cells and BSH, respectively. In addition, the higher the administered concentrations were, the smaller the CBE values became, with a clearer tendency in the use of BPA than BSH. The values for neutron capture agents that deliver into solid tumors more dependently on uptake capacity of tumor cells became more changeable.
  
  
  CONCLUSIONS
  Tumor characteristics, such as micro-environmental heterogeneity, stochastic genetic or epigenetic changes, or hierarchical organization of tumor cells, are thought to partially influence on the value of CBE, meaning that the CBE value itself may be one of the indices showing the degree of tumor heterogeneity.
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Shin-Ichiro
authors: S
authors: Masunaga
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Yoshinori
authors: Y
authors: Sakurai
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Hiroki
authors: H
authors: Tanaka
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Keizo
authors: K
authors: Tano
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Minoru
authors: M
authors: Suzuki
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Natsuko
authors: N
authors: Kondo
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Masaru
authors: M
authors: Narabayashi
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Yosuke
authors: Y
authors: Nakagawa
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Tsubasa
authors: T
authors: Watanabe
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Akira
authors: A
authors: Maruhashi
authors: Particle Radiation Biology, Department of Radiation Life and Medical Science, Research Reactor Institute, Kyoto University, 2-1010, Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494 Japan.
authors: Koji
authors: K
authors: Ono
keywords: Boron neutron capture therapy; Compound biological effectiveness; Neutron capture agent; Quiescent cell; Relative biological effectiveness; Tumor heterogeneity