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

Journal of Nuclear Medicine

Roger W. Howell¹  Prasad V.S.V. Neti¹ 

关键词: ¹³¹I;    iodine-131;    iododeoxyuridine;    cellular dosimetry;    multicellular cluster;    V79 cells;    survival;    ionizing radiation;    β-particles;    radiation effects;    adverse effects;    therapeutic use;    fluorescence-activated cell sorting;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 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. Methods: A 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. Results: The unlabeled cells, which received only a cross-dose, exhibited a mean lethal dose D37 of 4.0 ± 0.3 Gy. In contrast, the labeled cells received both a self-dose and a cross-dose. Isolating the effects of the self-dose resulted in a D37 of 1.2 ± 0.3 Gy, which was about 3.3 times more toxic per unit dose than the cross-dose. The reason for these differences appears to be primarily related to the higher relative biological effectiveness of the self-dose delivered by 131IdU compared with the cross-dose. Theoretical modeling of the killing of labeled and unlabeled cells was achieved by considering the cellular self-doses and cross-doses. Conclusion: Cellular self-doses and cross-doses play an important role in determining the biological response of tissue to microscopic nonuniform distributions of 131I. Prediction of the biological response requires that both self-doses and cross-doses be considered along with their relative lethality per unit dose.

【 授权许可】

Unknown