Evidence of Local Concentration of α-Particles from (211)At-Labeled Antibodies in Liver Metastasis Tissue.

Evidence of Local Concentration of α-Particles from (211)At-Labeled Antibodies in Liver Metastasis Tissue.
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DOI:
10.2967/jnumed.118.216853
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发表时间:
2019-04
期刊:
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子:
--
通讯作者:
Hasegawa S
Hasegawa S
中科院分区:
其他
文献类型:
--
作者:
Kodaira S;Morokoshi Y;Li HK;Konishi T;Kurano M;Hasegawa S

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我们研究了211 At标记的曲妥珠单抗抗抗人表皮生长因子受体2型抗原的α颗粒在小鼠肝转移组织中的局部浓度。方法:采用~(211)At-核素对小鼠肝转移癌进行腹腔注射。12小时后,取出肝脏并切片,将2份无病变的肝组织和1份含有转移性病变的肝组织样品固定在CR-39塑料核径迹探测器上。采集CR-39上组织的显微镜图像。照射31小时后,从CR-39中取出组织。CR-39上α粒子径迹的显微图像是在化学蚀刻后获得的。将每个组织样本的位置和发射的α粒子轨迹调整到相同的坐标。结果:211 At发射的α粒子径迹在组织内的位置分布是一致的。α粒子径迹主要分布在组织的肿瘤区域。通过对线性能量转移谱的光谱分析,获得了以10 μm为间隔的单个细胞的吸收剂量。浓度效率-肿瘤区域坏死组织中α粒子径迹与正常组织中α粒子径迹的径迹密度比-为6.0 ± 0.2。在肿瘤区域,高线性能量转移的α粒子沉积了足够大的剂量,对癌细胞造成致命损伤。结论:总吸收剂量范围为1 ~ 7戈伊,峰值约为2戈伊,由于211 At发射的α粒子具有较高的相对生物学效应,因此相当于生物等效剂量的2-3倍。
We investigated the local concentration of α-particles from 211At-labeled trastuzumab antibodies against human epidermal growth factor receptor type 2 antigens in liver metastasis tissue of mice. Methods: Mice carrying metastatic cancer in their liver were injected with 211At-agent. After 12 h, the liver was removed and sliced, and 2 tissue samples of liver tissues without lesions and one containing metastatic lesions were mounted on the CR-39 plastic nuclear track detector. Microscope images of the tissues on the CR-39 were acquired. After irradiation for 31 h, the tissues were removed from the CR-39. A microscope image of α-particle tracks on the CR-39 was acquired after chemical etching. The positions of each tissue sample and the emitted α-particle tracks were adjusted to the same coordinates. Results: The positional distribution of α-particle tracks emitted from 211At was consistent within the tissue. The α-particle tracks were mainly allocated in the tumor region of the tissue. The absorbed dose in individual cells segmented by 10-μm intervals was obtained by the spectroscopic analysis of the linear-energy-transfer spectrum. The concentration efficiency—the track density ratio of α-particle tracks in the necrotized tissue, which was the tumor region, to the normal tissue—was found to be 6.0 ± 0.2. In the tumor region, the high–linear-energy-transfer α-particles deposited a large enough dose to cause lethal damage to the cancer cells. Conclusion: The total absorbed dose ranged from 1 to 7 Gy with a peak at around 2 Gy, which would correspond to a 2–3 times higher biologically equivalent dose because of the high relative biological effectiveness of the α-particles emitted from 211At.
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