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Decreased radioiodine uptake of FRTL-5 cells after 131I incubation in vitro: molecular biological investigations indicate a cell cycle-dependent pathway

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

In radioiodine therapy the “stunning phenomenon” is defined as a reduction of radioiodine uptake after diagnostic application of 131I. In the current study, we established an in vitro model based on the “Fisher rat thyrocyte cell line no. 5” (FRTL-5) to investigate the stunning.

Methods

TSH-stimulated FRTL-5 cells were incubated with 131I. Time-dependent 131I uptake and the viability of FRTL-5 cells were evaluated at 4–144 h after radioiodine application. All data was corrected for number of viable cells, half life and 131I concentration. Sodium iodide symporter (NIS) and the housekeeping gene (β-actin, GAPDH) levels were quantified by quantitative polymerase chain reaction (qPCR). Additionally, immunohistochemical staining (IHC) of NIS on the cell membrane was carried out.

Results

FRTL-5 monolayer cell cultures showed a specific maximum uptake of 131I 24–48 h after application. Significantly decreased 131I uptake values were observed after 72–144 h. The decrease in radioiodine uptake was correlated with decreasing mRNA levels of NIS and housekeeping genes. In parallel, unlike in controls, IHC staining of NIS on FRTL-5 cells declined significantly after 131I long-term incubation.

Conclusions

It could be demonstrated that during 131I incubation of FRTL-5 cells, radioiodine uptake decreased significantly. Simultaneously decreasing levels of NIS mRNA and protein expression suggest a NIS-associated mechanism. Since mRNA levels of housekeeping genes decreased, too, the reduced NIS expression might be provoked by a cell cycle arrest. Our investigations recommend the FRTL-5 model as a valuable tool for further molecular biological investigations of the stunning phenomenon.

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Acknowledgements

The authors thank Silvia Grammerstorf-Rosche, Angela Oldörp and Detlev Schult for technical assistance. This work was supported in parts by ‘Margarete Markus Charity Foundation’.

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Authors and Affiliations

  1. Clinic of Radiology and Nuclear Medicine, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Birgit Meller, Wibke Deisting & Manfred Baehre

  2. Clinic of Internal Medicine I, University of Lübeck, Lübeck, Germany

    Erzsébet Gaspar & Björn E. Wenzel

  3. Department of Clinical Biochemistry and Molecular Biology, Medical Centre of Postgraduate Education, Warsaw, Poland

    Barbara Czarnocka

Authors
  1. Birgit Meller
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  2. Erzsébet Gaspar
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  3. Wibke Deisting
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  6. Björn E. Wenzel
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Correspondence to Birgit Meller.

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Meller, B., Gaspar, E., Deisting, W. et al. Decreased radioiodine uptake of FRTL-5 cells after 131I incubation in vitro: molecular biological investigations indicate a cell cycle-dependent pathway. Eur J Nucl Med Mol Imaging 35, 1204–1212 (2008). https://doi.org/10.1007/s00259-007-0666-0

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