Radiation doses to the cell nucleus in single cells and cells in micrometastases in targeted therapy with 131I labeled ligands or antibodies

Radiation doses to the cell nucleus in single cells and cells in micrometastases in targeted therapy with 131I labeled ligands or antibodies
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DOI:
10.1016/s0360-3016(99)00476-9
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发表时间:
2000-03-01
影响因子:
7
通讯作者:
Carlsson, J
Carlsson, J
中科院分区:
医学1区
文献类型:
--
作者:
Hartman, T;Lundqvist, H;Carlsson, J

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目的:从理论上探讨核辐射剂量与I-131亚细胞位置的关系。还研究了细胞大小和交叉照射对细胞簇的影响。方法与材料:利用描述I-131点源周围剂量率的数据,计算了不同尺寸细胞模型内部和周围的剂量分布。假设的I-131位置是在细胞膜或核膜上,在细胞质中,在细胞核中,或在整个细胞中扩散。利用剂量分布计算靶细胞核和邻近细胞核的平均剂量。结果:单个靶细胞内剂量分布随I-131亚细胞位置的不同呈现出不同的分布曲线。以细胞核为靶点而不是细胞膜,可以使对细胞核的剂量增加10倍。交叉火力照射可能是6个以上细胞群的核剂量的主要来源。结论:对于暴露于I-131的弥散性或聚集性肿瘤细胞的靶向放射性核素治疗,不考虑显微镜的剂量法是不够的。即使在单个细胞中,当I-131位于细胞核附近或细胞核内,或者当簇足够大时,也可以达到治疗剂量。(C) 2000 Elsevier Science Inc.;
Purpose: The aim of this study was to theoretically investigate how the radiation dose to cell nuclei depends on the subcellular position of I-131. The influence of the size of the cells and crossfire irradiation in clusters of cells was also studied.Methods and Material: Using data describing the dose rate around a point source of I-131, We calculated the dose distributions inside and around cell models of different sizes. The assumed positions of I-131 were on the cellular or nuclear membrane, in the cytoplasm, in the nucleus, or spread in the whole cell. The mean doses to the nucleus of the targeted cell and to the nuclei of its neighbors were calculated using the dose distributions.Results: The dose distributions inside a single targeted cell showed very different distribution profiles depending on the subcellular position of the I-131. Targeting the nucleus instead of the cellular membrane could increase the dose to the nucleus 10-fold. Crossfire irradiation can be the major contributor to the nuclear dose in clusters of more than six cells.Conclusions: Dosimetry without microscopic considerations is inadequate for targeted radionuclide therapy of disseminated or clustering tumor cells exposed to I-131. Therapeutic doses could be achieved, even in single cells, when I-131 was positioned near, or inside the cell nucleus, or when the clusters were large enough. (C) 2000 Elsevier Science Inc.