Neti Prasad V S V, Howell Roger W
Division of Radiation Research, Department of Radiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
J Nucl Med. 2003 Dec;44(12):2019-26.
To varying degrees, radiopharmaceuticals are distributed nonuniformly in tissue. At a macroscopic level, the radiopharmaceutical may appear to be uniformly distributed throughout the tissue. However, on closer inspection, not all cells in the tissue may be labeled with the radiopharmaceutical. Furthermore, the radioactivity in the cells may be localized only in certain compartments within the cell. This work uses a cell culture model to examine the impact of nonuniformity at the multicellular level on the lethal effects of (131)I.
A 3-dimensional tissue culture model was used to investigate the biologic effects of nonuniform distributions of (131)I in a large population of mammalian cells. Chinese hamster V79 cells were labeled with (131)I-iododeoxyuridine ((131)IdU), mixed with unlabeled cells, and multicellular clusters (4 x 10(6) cells) were formed by gentle centrifugation. Thus, the labeled cells were randomly located in the cluster to achieve a uniform distribution of radioactivity at the macroscopic level, yet nonuniform at the multicellular level. The clusters were assembled as described and then maintained at 10.5 degrees C for 72 h to allow (131)I decays to accumulate. The clusters were then dismantled and the cells were plated for colony formation.
When 100% of the cells were labeled, the surviving fraction of cells in the cluster was exponentially dependent on the cluster activity down to 0.1% survival. In contrast, when 10% of the cells were labeled, it was observed that the survival fraction begins to saturate at about 1% survival. Absorbed-dose estimates reveal that the mean lethal cluster dose is 4.5, 5.7, and 6.4 Gy for 100%, 10%, and 1% labeling, respectively.
These data indicate that when the distribution of (131)I is uniform at the macroscopic level, but nonuniform at the multicellular level, the mean absorbed dose to a tissue element may not be a suitable quantity for use in predicting biologic effect. Rather, cellular and multicellular dosimetry approaches may be necessary to predict the biologic effects of incorporated (131)I.
放射性药物在组织中的分布程度各不相同，在宏观层面上，放射性药物可能看起来在整个组织中均匀分布。然而，仔细观察会发现，组织中的并非所有细胞都会被放射性药物标记。此外，细胞中的放射性可能仅局限于细胞内的某些区室。这项研究使用细胞培养模型来研究多细胞水平的不均匀性对¹³¹I致死效应的影响。
使用三维组织培养模型研究¹³¹I在大量哺乳动物细胞中的不均匀分布的生物学效应。用¹³¹I-碘脱氧尿苷（¹³¹IdU）标记中国仓鼠V79细胞，与未标记的细胞混合，通过轻轻离心形成多细胞簇（4×10⁶个细胞）。这样，标记的细胞随机分布在簇中，以在宏观层面实现放射性的均匀分布，但在多细胞层面则不均匀。按照所述方法组装簇，然后在10.5℃下维持72小时，以使¹³¹I衰变积累。然后拆解簇，将细胞接种以形成集落。
当100%的细胞被标记时，簇中细胞的存活分数呈指数依赖于簇的活性，直至存活至0.1%。相比之下，当10%的细胞被标记时，观察到存活分数在约1%存活时开始饱和。吸收剂量估计显示，对于100%、10%和1%的标记，平均致死簇剂量分别为4.5、5.7和6.4 Gy。
这些数据表明，当¹³¹I的分布在宏观层面均匀但在多细胞层面不均匀时，组织单元的平均吸收剂量可能不是预测生物学效应的合适量度。相反，可能需要细胞和多细胞剂量测定方法来预测掺入¹³¹I的生物学效应。
