Statistical and radiobiological analysis of the so-called thyroid stunning

The origin of the reduction in thyroid uptake after a low activity iodine scan, so-called stunning effect, is still controversial. Two explanations prevail: an individual cell stunning that reduces its capability to store iodine without altering its viability, and/or a significant cell-killing fraction that reduces the number of cells in the tissue still taking up iodine. Our aim is to analyze whether this last assumption could explain the observed reduction.

The survival fraction after administration of a small radioiodine activity was computed by two independent methods: the application of the statistical theory underlying tissue control probability on recent clinical studies of thyroid remnant (131)I ablation and the use of the radiosensitivities reported in human thyroid cell assays for different radioiodine isotopes.

Both methods provided survival fractions in line with the uptake reduction observed after a low (131)I activity scan. The second method also predicts a similar behavior after a low (123)I or (124)I activity scan.

This study shows that the cell-killing fraction is sufficient to explain the uptake reduction effect for (131)I and (123)I after a low activity scan and that even if some still living cells express a stunning effect just after irradiation (as shown in vitro), they will mostly die with time. As the β/α value is very low, this therapy fractionation should not impact the patient outcome in agreement with recent studies. However, in case of huge uptake heterogeneity, pre-therapy scan could specifically kills high-uptake cells and by the way could reduce the cross irradiation to the low-uptake cells during the therapy, resulting in a reduction of the ablation success rate.