When may a nonuniform distribution of 131I be considered uniform? An experimental basis for multicellular dosimetry.

Abstract

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.