Modeling principles of protective thyroid blocking

Abstract

Purpose

In the case of a nuclear incident, the release of radioiodine must be expected. Radioiodine accumulates in the thyroid and by irradiation enhances the risk of cancer. Large doses of stable (non-radioactive) iodine may inhibit radioiodine accumulation and protect the thyroid (‘thyroid blocking’). Protection is based on a competition at the active carrier site in the cellular membrane and an additional temporary inhibition of the organification of iodide (Wolff-Chaikoff effect). Alternatively, other agents like e.g. perchlorate that compete with iodide for the uptake into the thyrocytes may also confer thyroidal protection against radioiodine exposure.

Biokinetic models for radioiodine mostly describe exchanges between compartments by first order kinetics. This leads to correct predictions only for low (radio)iodide concentrations. These models are not suited to describe the kinetics of iodine if administered at the dosages recommended for thyroid blocking and moreover does not permit to simulate either the protective competition mechanism at the membrane or the Wolff-Chaikoff effect. Models adapted for this purpose must be used. Such models may use a mathematical relation between the serum iodide concentration and a relative uptake suppression or a dependent rate constant determining total thyroidal radioiodine accumulation. Alternatively, the thyroidal uptake rate constant may be modeled as a function of the total iodine content of the gland relative to a saturation amount. Newer models integrate a carrier-mechanism described by Michalis-Menten kinetics in the membrane and in analogy to enzyme kinetics apply the rate law for monomolecular irreversible enzyme reactions with competing substrates to model the competition mechanism. An additional total iodide uptake block, independent on competition but limited in time, is used to simulate the Wolff-Chaikoff effect.

Conclusion

The selection of the best model depends on the issue to be studied. Most models cannot quantify the relative contributions of the competition mechanism at the membrane and the Wolff-Chaikoff effect. This makes it impossible or exceedingly difficult to simulate prolonged radioiodine exposure and the effect of repetitive administrations of stable iodine. The newer thyroid blocking models with a separate modeling of competition and Wolff-Chaikoff effect allow better quantitative mechanistic insights and offer the possibility to simulate complex radioiodine exposure scenarios and various protective dosage schemes of stable iodine relatively easily. Moreover, they permit to study the protective effects of other competitors at the membrane carrier site, like e.g. perchlorate, and to draw conclusions on their protective efficacy in comparison to stable iodine.

Keywords:

• Medical NRBC-protection
• nuclear and radiological emergency
• radioiodine
• thyroidal protection modeling
• iodine blockade
• perchlorate

Ethics approval

Not applicable. This article does not contain any studies with human or animal subjects.

Consent to participate

Not applicable. This article does not contain any studies with humans.

Consent for publication

All authors have approved the publication of this study.

Author contributions

All authors have contributed to the study.

Disclosure statement

The authors declare that they have no conflicts of interest.

Data availability statement

Not applicable. This paper is based on published literature given in the text.

Additional information

Notes on contributors

Alexis Rump

Alexis Rump, MD, PhD, MHBA, is anesthesiologist and clinical pharmacologist and currently assigned at the Institute of Radiobiology of the Bundeswehr in Munich.

Stefan Eder

Stephan Eder, MD, and Andreas Lamkowski, MD, are physicians, specialists in occupational medicine and researchers in the field of radiobiology.

Cornelius Hermann

Cornelius Hermann is pharmacist and researcher in radiobiology.

Andreas Lamkowski

Andreas Lamkowski is a physician, specialist in occupational medicine and a researcher at the Bundeswehr Institute for radiobiology.

Manabu Kinoshita

Manabu Kinoshita, MD, PhD is professor at the National Defense Medical College in Tokorozawa (Japan) and specialist in the field of radiobiology.

Tetsuo Yamamoto

Testsuo Yamamoto, MD, PhD, is the commanding officer of the NBC Countermeasure Medical Unit of the Japan Ground Self Defense Forces.

Junya Take

Junya Take, MD, is specialist in pediatrics at the National Defense Medical College Hospital and a researcher in the field of radiobiology. 

Michael Abend

Michael Abend, MD, PhD, MSc, is professor in radiobiology and the deputy director of the Bundeswehr Institute of Radiobiology.

Nariyoshi Shinomiya

Nariyoshi Shinomiya, MD, PhD is professor and the president of the National Defense Medical College.

Matthias Port

Matthias Port, MD, PhD is professor of internal medicine (hematology/oncology) and radiobiology and the director of the Bundeswehr Institute of Radiobiology.