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

The dependency of compound biological effectiveness factors on the type and the concentration of administered neutron capture agents in boron neutron capture therapy.
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DOI:
10.1186/2193-1801-3-128
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发表时间:
2014
期刊:
影响因子:
--
通讯作者:
Ono K
Ono K
中科院分区:
其他
文献类型:
--
作者:
Masunaga S;Sakurai Y;Tanaka H;Tano K;Suzuki M;Kondo N;Narabayashi M;Nakagawa Y;Watanabe T;Maruhashi A;Ono K

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探讨中子俘获剂种类和浓度对硼中子俘获治疗中复合生物学效应(CBE)值的影响。在皮下施用3种不同浓度的10 B-载体硼苯丙氨酸-10B(BPA)或巯基十二硼酸钠-10B(BSH)后,通过γ射线光谱法测量肿瘤中的10 B浓度。用5-溴-2 ′-脱氧尿苷(BrdU)连续标记SCC VII荷瘤C3 H/He小鼠瘤内所有增殖(P)细胞,然后用BPA或BSH处理。反应堆中子束照射后,在此期间肿瘤内10 B浓度保持在彼此相似的水平,立即从一些肿瘤中分离细胞,并与胞质分裂阻滞剂一起孵育。使用BrdU免疫荧光染色,基于微核率评估BrdU未标记静止(Q)和总(= P + Q)肿瘤细胞的反应。CBE值在Q细胞和BPA的使用中分别高于总细胞和BSH。此外,给药浓度越高,CBE值越小,BPA的使用趋势比BSH更明显。递送到实体肿瘤中的中子捕获剂的值更依赖于肿瘤细胞的摄取能力变得更易变化。肿瘤特征,如微环境异质性,随机遗传或表观遗传变化,或肿瘤细胞的分层组织,被认为部分影响CBE值,这意味着CBE值本身可能是显示肿瘤异质性程度的指标之一。
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. After 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. 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. 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.
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