Isolating effects of microscopic nonuniform distributions of 131I on labeled and unlabeled cells

Prasad V.S.V. Neti, Roger W. Howell

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30 Scopus citations


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 10.5̊C 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 D 37 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.

Original languageEnglish (US)
Pages (from-to)1050-1058
Number of pages9
JournalJournal of Nuclear Medicine
Issue number6
StatePublished - Jun 1 2004

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging


  • Adverse effects
  • Cellular dosimetry
  • Fluorescence-activated cell sorting
  • I
  • Iodine-131
  • Iododeoxyuridine
  • Ionizing radiation
  • Multicellular cluster
  • Radiation effects
  • Survival
  • Therapeutic use
  • V79 cells
  • β-particles


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