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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 (MN) frequencies (b) afterin vivoirradiation using neutron beams without the10B-carrier as 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” and with “neutrons only” are shown at left and right panels, respectively. Bars represent standard errors (n = 9).
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Fig3: Cell survival curves (a) and the net micronucleus (MN) frequencies (b) afterin vivoirradiation using neutron beams without the10B-carrier as 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” and with “neutrons only” are shown at left and right panels, respectively. Bars represent standard errors (n = 9).

Mentions: Figure 3(a) and (b) show cell survival curves and the net MN frequencies after in vivo irradiation using neutron beams without the 10B-carrier, respectively. In terms of the net MN frequency, the difference in radio-sensitivity between total and Q tumor cells was apparently reduced compared with irradiation with γ-rays only. To obtain data on cell survival and the net MN frequency for “neutrons only” without the 10B-carrier, the data for “neutron beams” without the 10B-carrier were normalized with the above-mentioned data for irradiation with γ-rays only. The cell survival for “neutrons only” without the 10B-carrier was expressed as a function of ln SF = - 0.3384 D – 0.0121 D2. The net MN frequencies for “neutrons only” without the 10B-carrier in total and Q tumor cells were expressed as a function of Net MN frT = 0.1119 D + 0.0074 D2 and Net MN frQ = 0.0837 D + 0.0135 D2, respectively.Figure 3


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 (MN) frequencies (b) afterin vivoirradiation using neutron beams without the10B-carrier as 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” and with “neutrons only” are shown at left 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

Fig3: Cell survival curves (a) and the net micronucleus (MN) frequencies (b) afterin vivoirradiation using neutron beams without the10B-carrier as 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” and with “neutrons only” are shown at left and right panels, respectively. Bars represent standard errors (n = 9).
Mentions: Figure 3(a) and (b) show cell survival curves and the net MN frequencies after in vivo irradiation using neutron beams without the 10B-carrier, respectively. In terms of the net MN frequency, the difference in radio-sensitivity between total and Q tumor cells was apparently reduced compared with irradiation with γ-rays only. To obtain data on cell survival and the net MN frequency for “neutrons only” without the 10B-carrier, the data for “neutron beams” without the 10B-carrier were normalized with the above-mentioned data for irradiation with γ-rays only. The cell survival for “neutrons only” without the 10B-carrier was expressed as a function of ln SF = - 0.3384 D – 0.0121 D2. The net MN frequencies for “neutrons only” without the 10B-carrier in total and Q tumor cells were expressed as a function of Net MN frT = 0.1119 D + 0.0074 D2 and Net MN frQ = 0.0837 D + 0.0135 D2, respectively.Figure 3

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