Isolating Effects of Microscopic Nonuniform Distributions of 131I on Labeled and Unlabeled Cells

摘要

Radiopharmaceuticals are generally distributed nonuniformly in tissue. At the microscopic level, only a fraction of the cells in tissue are labeled. Consequently, the labeled cells receive an absorbed dose from radioactivity within the cell (self-dose) as well as an absorbed dose from radioactivity in surrounding cells (cross-dose). On the other hand, unlabeled cells only receive a cross-dose. This work uses a novel approach to examine the lethal effects of microscopic nonuniformities of ¹³¹I individually on the labeled and unlabeled cells.MethodsA multicellular tissue model was used to investigate the lethality of microscopic nonuniform distributions of ¹³¹I. Mammalian cells (V79) were dyed with CFDA-SE (carboxy fluorescein diacetate succinimidyl ester) and labeled with ¹³¹I-iododeoxyuridine (¹³¹IdU). The dyed labeled cells were then mixed with equal numbers of unlabeled cells, and 3-dimensional tissue constructs (4 × 10⁶ cells) were formed by centrifugation in a small tube. This resulted in a uniform distribution of ¹³¹I at the macroscopic level but nonuniform distribution at the multicellular level, wherein 50% of the cells were labeled. The multicellular clusters were maintained at 10.5°C for 72 h to allow ¹³¹I decays to accumulate. The clusters were then dismantled and the labeled (dyed) and unlabeled (undyed) cells were separately seeded for colony formation using a fluorescence-activated cell sorter.