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The dependency of compound biological effectiveness factors on the type and the concentration of administered neutron capture agents in boron neutron capture therapy.

Masunaga S, Sakurai Y, Tanaka H, Tano K, Suzuki M, Kondo N, Narabayashi M, Nakagawa Y, Watanabe T, Maruhashi A, Ono K - Springerplus (2014)

Bottom Line: 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.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.The CBE values were higher in Q cells and in the use of BPA than total cells and BSH, respectively.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT

Purpose: 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 and materials: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Cell survival curves (a) and the net micronucleus frequencies (b) afterin vivoirradiation using neutron beams following subcutaneous administration of sodium mercaptododecaborate-10B at dose of 125 (circles), 250 (triangles), or 375 (squares) mg·kg-1as a function of the physical radiation dose in total (open symbols) and quiescent (Q, (solid symbols)) tumor cell populations. The data for irradiation with reactor “neutron beams”, with “neutrons only”, and at the “10B dose” are shown at the left, central, and right panels, respectively. Bars represent standard errors (n = 9).
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Fig5: Cell survival curves (a) and the net micronucleus frequencies (b) afterin vivoirradiation using neutron beams following subcutaneous administration of sodium mercaptododecaborate-10B at dose of 125 (circles), 250 (triangles), or 375 (squares) mg·kg-1as a function of the physical radiation dose in total (open symbols) and quiescent (Q, (solid symbols)) tumor cell populations. The data for irradiation with reactor “neutron beams”, with “neutrons only”, and at the “10B dose” are shown at the left, central, and right panels, respectively. Bars represent standard errors (n = 9).

Mentions: The data on cell survival and the net MN frequency for irradiation with “neutron beams” with the 10B-carrier were normalized with the data for irradiation with γ-rays only, then further normalized with the data for irradiation with “neutrons only” without the 10B-carrier in order to obtain data for irradiation at the “10B dose”. Figure 4(a) and (b) show cell survival curves and the net MN frequencies in the function of physically absorbed radiation dose after in vivo irradiation using neutron beams following BPA administration, respectively. Figure 5(a) and (b) show cell survival curves and the net MN frequencies in the function of physically absorbed radiation dose after in vivo irradiation using neutron beams following BSH administration, respectively. In Figures 4 and5, the data for irradiation with available reactor “neutron beams” including γ-rays, with “neutrons only” excluding contribution of γ-rays, and with “10B dose” further excluding contribution of neutrons in the absence of 10B, that is to say, the physically absorbed dose truly originating from high LET, heavier-charged α particles and 7Li ions released as products of the thermal neutron capture and fission reactions with 10B [10B(n,α)7Li] only in the presence of 10B are shown left, central and right panels, respectively. Whichever 10B-carrier was employed, the radio-sensitivity was decreased as the concentration of administered 10B-carrier increased. In addition, this tendency was more clearly observed when using BPA than BSH and in Q than in the total tumor cell population.Figure 4


The dependency of compound biological effectiveness factors on the type and the concentration of administered neutron capture agents in boron neutron capture therapy.

Masunaga S, Sakurai Y, Tanaka H, Tano K, Suzuki M, Kondo N, Narabayashi M, Nakagawa Y, Watanabe T, Maruhashi A, Ono K - Springerplus (2014)

Cell survival curves (a) and the net micronucleus frequencies (b) afterin vivoirradiation using neutron beams following subcutaneous administration of sodium mercaptododecaborate-10B at dose of 125 (circles), 250 (triangles), or 375 (squares) mg·kg-1as a function of the physical radiation dose in total (open symbols) and quiescent (Q, (solid symbols)) tumor cell populations. The data for irradiation with reactor “neutron beams”, with “neutrons only”, and at the “10B dose” are shown at the left, central, and right panels, respectively. Bars represent standard errors (n = 9).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4320213&req=5

Fig5: Cell survival curves (a) and the net micronucleus frequencies (b) afterin vivoirradiation using neutron beams following subcutaneous administration of sodium mercaptododecaborate-10B at dose of 125 (circles), 250 (triangles), or 375 (squares) mg·kg-1as a function of the physical radiation dose in total (open symbols) and quiescent (Q, (solid symbols)) tumor cell populations. The data for irradiation with reactor “neutron beams”, with “neutrons only”, and at the “10B dose” are shown at the left, central, and right panels, respectively. Bars represent standard errors (n = 9).
Mentions: The data on cell survival and the net MN frequency for irradiation with “neutron beams” with the 10B-carrier were normalized with the data for irradiation with γ-rays only, then further normalized with the data for irradiation with “neutrons only” without the 10B-carrier in order to obtain data for irradiation at the “10B dose”. Figure 4(a) and (b) show cell survival curves and the net MN frequencies in the function of physically absorbed radiation dose after in vivo irradiation using neutron beams following BPA administration, respectively. Figure 5(a) and (b) show cell survival curves and the net MN frequencies in the function of physically absorbed radiation dose after in vivo irradiation using neutron beams following BSH administration, respectively. In Figures 4 and5, the data for irradiation with available reactor “neutron beams” including γ-rays, with “neutrons only” excluding contribution of γ-rays, and with “10B dose” further excluding contribution of neutrons in the absence of 10B, that is to say, the physically absorbed dose truly originating from high LET, heavier-charged α particles and 7Li ions released as products of the thermal neutron capture and fission reactions with 10B [10B(n,α)7Li] only in the presence of 10B are shown left, central and right panels, respectively. Whichever 10B-carrier was employed, the radio-sensitivity was decreased as the concentration of administered 10B-carrier increased. In addition, this tendency was more clearly observed when using BPA than BSH and in Q than in the total tumor cell population.Figure 4

Bottom Line: 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.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.The CBE values were higher in Q cells and in the use of BPA than total cells and BSH, respectively.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT

Purpose: 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 and materials: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus