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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

Time course of changes in10B concentrations in the solid tumors (a) and blood collected from the hearts (b) of SCC VII tumor-bearing mice after subcutaneous administration of each10B-carrier. Left panel of (a) shows time course of changes in tumors following administration of boronophenylalanine-10B at doses of 250 (●), 500 (▲), or 750 (■) mg·kg−1. Right panel of (a) shows time course of changes in tumors following administration of sodium mercaptododecaborate-10B at doses of 125 (●), 250 (▲), or 375 (■) mg·kg−1. (b) shows time course of changes in blood following administration of each 10B-carrier. Solid lines represent boronophenylalanine-10B at the doses of 250 (○), 500 (△), or 750 (□) mg·kg−1. Dotted lines represent sodium mercaptododecaborate-10B at doses of 125 (○), 250 (△), or 375 (□) mg·kg−1. Bars represent standard errors.
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Fig1: Time course of changes in10B concentrations in the solid tumors (a) and blood collected from the hearts (b) of SCC VII tumor-bearing mice after subcutaneous administration of each10B-carrier. Left panel of (a) shows time course of changes in tumors following administration of boronophenylalanine-10B at doses of 250 (●), 500 (▲), or 750 (■) mg·kg−1. Right panel of (a) shows time course of changes in tumors following administration of sodium mercaptododecaborate-10B at doses of 125 (●), 250 (▲), or 375 (■) mg·kg−1. (b) shows time course of changes in blood following administration of each 10B-carrier. Solid lines represent boronophenylalanine-10B at the doses of 250 (○), 500 (△), or 750 (□) mg·kg−1. Dotted lines represent sodium mercaptododecaborate-10B at doses of 125 (○), 250 (△), or 375 (□) mg·kg−1. Bars represent standard errors.

Mentions: Figure 1(a) and (b) show the time course of change in the values of the 10B concentration in solid tumors and blood, respectively. On the whole, the concentrations of 10B from both 10B-carriers, especially from BSH, in blood were higher than those in the tumors, and 10B from BSH in blood, that was higher than that from BPA, washed away much more rapidly than that from BPA. In contrast, the retention of 10B from the 10B-carriers in the tumors was similar except at 30 min after administration, when the concentration of 10B from BSH was much higher than that from BPA. As the administered doses of the 10B-carriers increased, higher concentrations of 10B in tumors and blood were observed. The 10B concentrations shown here were not thought to be especially toxic (Masunaga et al.2004).Figure 1


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)

Time course of changes in10B concentrations in the solid tumors (a) and blood collected from the hearts (b) of SCC VII tumor-bearing mice after subcutaneous administration of each10B-carrier. Left panel of (a) shows time course of changes in tumors following administration of boronophenylalanine-10B at doses of 250 (●), 500 (▲), or 750 (■) mg·kg−1. Right panel of (a) shows time course of changes in tumors following administration of sodium mercaptododecaborate-10B at doses of 125 (●), 250 (▲), or 375 (■) mg·kg−1. (b) shows time course of changes in blood following administration of each 10B-carrier. Solid lines represent boronophenylalanine-10B at the doses of 250 (○), 500 (△), or 750 (□) mg·kg−1. Dotted lines represent sodium mercaptododecaborate-10B at doses of 125 (○), 250 (△), or 375 (□) mg·kg−1. Bars represent standard errors.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Time course of changes in10B concentrations in the solid tumors (a) and blood collected from the hearts (b) of SCC VII tumor-bearing mice after subcutaneous administration of each10B-carrier. Left panel of (a) shows time course of changes in tumors following administration of boronophenylalanine-10B at doses of 250 (●), 500 (▲), or 750 (■) mg·kg−1. Right panel of (a) shows time course of changes in tumors following administration of sodium mercaptododecaborate-10B at doses of 125 (●), 250 (▲), or 375 (■) mg·kg−1. (b) shows time course of changes in blood following administration of each 10B-carrier. Solid lines represent boronophenylalanine-10B at the doses of 250 (○), 500 (△), or 750 (□) mg·kg−1. Dotted lines represent sodium mercaptododecaborate-10B at doses of 125 (○), 250 (△), or 375 (□) mg·kg−1. Bars represent standard errors.
Mentions: Figure 1(a) and (b) show the time course of change in the values of the 10B concentration in solid tumors and blood, respectively. On the whole, the concentrations of 10B from both 10B-carriers, especially from BSH, in blood were higher than those in the tumors, and 10B from BSH in blood, that was higher than that from BPA, washed away much more rapidly than that from BPA. In contrast, the retention of 10B from the 10B-carriers in the tumors was similar except at 30 min after administration, when the concentration of 10B from BSH was much higher than that from BPA. As the administered doses of the 10B-carriers increased, higher concentrations of 10B in tumors and blood were observed. The 10B concentrations shown here were not thought to be especially toxic (Masunaga et al.2004).Figure 1

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