Statistical and radiobiological analysis of the so-called thyroid stunning.

Stephan Walrand,François Jamar,Michel Hesse

doi:10.1186/s13550-015-0144-9

Abstract

BackgroundThe 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.MethodsThe 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 131I ablation and the use of the radiosensitivities reported in human thyroid cell assays for different radioiodine isotopes.ResultsBoth methods provided survival fractions in line with the uptake reduction observed after a low 131I activity scan. The second method also predicts a similar behavior after a low 123I or 124I activity scan.ConclusionsThis study shows that the cell-killing fraction is sufficient to explain the uptake reduction effect for 131I and 123I 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0144-9) contains supplementary material, which is available to authorized users.

Highlights

The origin of the reduction in thyroid uptake after a low activity iodine scan, so-called stunning effect, is still controversial
The so-called thyroid stunning effect refers to the observed fact that the 131I uptake at therapy is lower than the one predicted from a 131I pre-therapeutic scan, even when using a low activity such as 74 MBq [1,2,3,4,5,6,7]
Two independent formalisms show that the cell-killing fraction is sufficient to explain the observed iodine uptake reduction after a first pre-therapy scan, i.e., (1) a statistical analysis based on Poisson statistics and on the remnant control probability reported in recent clinical studies, and (2) a radiobiological analysis using normal and cancer thyroid cells radiosensitivity assays data jointly with the uptake non-uniformity observed in 124I PET

Summary

Introduction

The origin of the reduction in thyroid uptake after a low activity iodine scan, so-called stunning effect, is still controversial. In vitro studies suggest that irradiation may perturb cell metabolism before cell viability [15], by a downregulation of the sodium/iodide symporter (NIS) expression at the transcription level [16, 17], resulting in a reduction of the capacity to transport iodine. Others suggest that this reduction could purely result from killed cells that are no longer. A lower, but still actual uptake reduction was observed by Hilditch et al [6] after administering 200 MBq of 123I To explain this fact, the authors suggested a self-stunning effect occurring during the 131I therapy itself. The rationale is that in average 123I delivers 80 times less Gy per GBq than 131I due to its shorter half-life and its lower electron emission energy [18]

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