Abstract
PurposeTo 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 and materialsAfter the subcutaneous administration of a 10B-carrier, boronophenylalanine-10B (BPA) or sodium mercaptododecaborate-10B (BSH), at 3 separate concentrations, the 10B 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 10B 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.ResultsThe 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.ConclusionTumor 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.
Highlights
A neutron capture reaction in boron [10B(n, α)7Li] is, in principle, very effective in destroying tumors, provided that a sufficient amount of 10B can be accumulated in the target tumor and a sufficient number of very-lowenergy thermal neutrons can be delivered there
The compound biological effectiveness (CBE) values were higher in Q cells and in the use of BPA than total cells and BSH, respectively
The values for neutron capture agents that deliver into solid tumors more dependently on uptake capacity of tumor cells became more changeable
Summary
A neutron capture reaction in boron [10B(n, α)7Li] is, in principle, very effective in destroying tumors, provided that a sufficient amount of 10B can be accumulated in the target tumor and a sufficient number of very-lowenergy thermal neutrons can be delivered there. The two particles generated in this reaction have a high linear radiation This is called relative biological effectiveness (RBE), which is the ratio of the absorbed dose of a reference source of radiation (e.g., X-rays) to that of the test radiation that produces the same biological effect. Because both tumor and surrounding normal tissues are present in the radiation field, there will be an unavoidable, nonspecific background dose, consisting of both high and low LET radiation. A greater concentration of 10B in the tumor will result in receiving a much higher total dose than that of adjacent normal tissues. The total radiation dose delivered to any tissue can be expressed in photon equivalent units as the sum of each of the high LET dose components multiplied by weighting factors, which depend on the increased radiobiological effectiveness of each of these radiation components (Barth et al 2012)
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