Download PDF
CC BY-NC-ND 4.0 · Drug Res (Stuttg) 2019; 69(11): 583-597
DOI: 10.1055/a-0960-5590
Original Article
Eigentümer und Copyright ©Georg Thieme Verlag KG 2018

Development of New Biokinetic-Dosimetric Models for the Simulation of Iodine Blockade in the Case of Radioiodine Exposure in Man

Alexis Rump
1   Bundeswehr Institute of Radiobiology, Munich, Germany
,
Stefan Eder
1   Bundeswehr Institute of Radiobiology, Munich, Germany
,
Andreas Lamkowski
1   Bundeswehr Institute of Radiobiology, Munich, Germany
,
Manabu Kinoshita
2   Japan Self Defense Forces, National Defense Medical College Research Institute, Tokorozawa, Japan
,
Tetsuo Yamamoto
3   Japan Ground Self Defense Forces, Military Medicine Research Unit and Ministry of Defense Clinic, Tokyo, Japan
,
Michael Abend
1   Bundeswehr Institute of Radiobiology, Munich, Germany
,
Nariyoshi Shinomiya
2   Japan Self Defense Forces, National Defense Medical College Research Institute, Tokorozawa, Japan
,
Matthias Port
1   Bundeswehr Institute of Radiobiology, Munich, Germany
› Author Affiliations
Further Information

Publication History

received 13 February 2019

accepted 06 June 2019

Publication Date:
07 August 2019 (online)

Also available at
   Permissions and Reprints

Abstract

In the case of nuclear incidents, radioiodine may be liberated. After incorporation it accumulates in the thyroid and by internal irradiation enhances the risk of cancer occurrence. By administering a large dose of non-radioactive iodine the uptake of radioiodine into the gland can be inhibited (“iodine blockade”). Biokinetic models using first order kinetics are not suited to simulate iodine blockade, as the uptake into the gland is mediated by a saturable active transport. Therefore, we integrated an uptake mechanism described by a Michaelis-Menten kinetic into a simple ICRP biokinetic model. We moreover added a total uptake blocking mechanism representing the Wolff-Chaikoff effect becoming active when the gland is saturated with iodine. The validity of the model was ascertained by comparison with IMBA software. The competition of radioiodine and stable iodine at the membrane carrier site was modeled according to the rate law for monomolecular reactions for competing substrates. Our simulations show that competition for the uptake at the membrane carrier site accounts for about 60% and the saturation of the gland with iodine for over 35% of the total protective efficacy that exceeds 95%. Following acute radioiodine exposure, it is preferable to administer a single large dose of stable iodine. In the case of continuous radioiodine exposure, a single dose of stable iodine is less effective than after an acute exposure and splitting the total available dose and shortening the dosage intervals enhance efficacy. Model-based simulations may be a useful tool to develop antidote dosage schemes for uncommon emergencies.

Key words

Medical NRBC-protection - nuclear and radiological emergency - radioiodine - iodine blockade
 

  • References

  • 1 Wohni T. External doses from radioactive fallout: Dosimetry and levels. Submitted in partial fulfilment for the degree of Doktor ingenier. Department of Physics, Norwegian Institute of Technology, University of Trondheim; 1995
    Google Scholar
  • 2 Glasstone S, Dolan PJ. The effects of nuclear weapons. Third edition, Washington DC: The United States Department of Defense and the United States Department of Energy, US Governemt Printing Office; 1977
    Google Scholar
  • 3 Simon SL, Bouville A, Land CE. Fallout from nuclear weapons tests and cancer risks. American Scientist 2006; 94: 48-57
    CrossrefPubMedGoogle Scholar
  • 4 List RJ. World wide fallout from operation Castle. Washington DC: United States Department from Commerce; 1955
    Google Scholar
  • 5 Simon SL, Bouville A, Land CE. et al. Radiation doses and cancer risks in the Marshall islands associated with exposure to radioactive fallout from Bikini and Enewetak nuclear weapons tests: Summary. Health Phys 2010; 99: 105-123
    CrossrefPubMedGoogle Scholar
  • 6 Imanaka T, Hayashi G, Endo S. Comparison of the accident process, radioactivity release and ground contamination between Chernobyl and Fukushima-1. J Radiat Res 2015; 56: i56-i61
    CrossrefPubMedGoogle Scholar
  • 7 National Cancer Institute. Estimated exposure and thyroid doses report. Download on the internetpage: Get the facts about exposure to I-131 radiation. 2015; https://www.cancer.gov/about-cancer/causes-prevention/risk/radiation/i131-report-and-appendix
    PubMed
  • 8 Chabot G. Radiation basics. Fission, Fusion. Q10097 - Why are cesium-137, strontium-90, and iodine-131 the fission products that get most talked about when many more fission products are produced in reactors? Health Physics Society 2016; https://hps.org/publicinformation/ate/q10097.html
    PubMed
  • 9 Geoffroy B, Verger P, Le Guen B. Pharmacocinétique de l’iode: revue des connaissances utiles en radioprotection accidentelle. Radioprotection 2000; 35: 151-174
    CrossrefPubMedGoogle Scholar
  • 10 Verger P, Aurengo A, Geoffroy B. et al. Iodine kinetics and effectiveness of stable iodine prophylaxis after intake of radioactive iodine: A review. Thyroid. 2001; 11: 353-360
    CrossrefPubMedGoogle Scholar
  • 11 Agency for Toxic Substances and Disease Registry (ATDSR) . Toxicological profile for iodine. Atlanta: US Department of health and human services, Public Health Service, Agency for Toxic Substances and Disease Registry; 2004
    Google Scholar
  • 12 Kovari M. Effect of delay time on effectiveness of stable iodine prophylaxis after intake of radioiodine. J Radiol Prot 1994; 14: 131-136
    CrossrefPubMedGoogle Scholar
  • 13 Berson SA, Yalow RS, Sorrentino J. et al. The determination of thyroidal and renal plasma I-131 clearance rates as a routine diagnostic test of thyroid dysfunction. J Clin Invest 1952; 31: 141-158
    CrossrefPubMedGoogle Scholar
  • 14 Henriksen T, Hole EO, Sagstuen E. et al. (Biophysics Group at UiO). Radiation and health. University of Oslo, Faculty of mathematics and natural sciences, Department of physics; 2014
    Google Scholar
  • 15 Rump A, Stricklin D, Lamkowski A. et al. Reconsidering current decorporation strategies after incorporation of radionuclides. Health Phys 2016; 111: 201-208
    PubMedGoogle Scholar
  • 16 World Health Organization (WHO) . Iodine thyroid blocking. Guidelines for use in planning for and responding to radiological and nuclear emergencies. Geneva: World Health Organization; 2017
    Google Scholar
  • 17 Autorité de Sureté Nucléaire (ASN). Guide national. Intervention médicale en cas d’évènement nucléaire ou radiologique. Version V 3.6 2008
    PubMed
  • 18 Strahlenschutzkommission (SSK). Verwendung von Jodtabletten zur Jodblockade der Schilddrüse bei einem Notfall mit Freisetzung von radioaktivem Jod Empfehlung der Strahlenschutzkommission. Verabschiedet in der 294. Sitzung der Strahlenschutzkommission am 26April 2018 https://www.ssk.de/SharedDocs/Beratungsergebnisse_PDF/2018/2018-04-26Jodmerk.pdf?__blob=publicationFile
    PubMed
  • 19 Wolff J, Chaikoff IL. Plasma inorganic iodide as a homeostatic regulator of thyroid function. J Biol Chem 1948; 174: 555-564
    CrossrefPubMedGoogle Scholar
  • 20 Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol 2014; Mar 10: 136-142
    CrossrefPubMedGoogle Scholar
  • 21 Riggs DS. Quantitative aspects of iodine metabolism. Pharmacol Rev 1952; 4: 284-370
    PubMedGoogle Scholar
  • 22 International Commission on Radiological Protection (ICRP) . Dose coefficients 3279 for intakes of radionuclides by workers. ICRP Publication 68. Oxford: Pergamon Press; 1994
    Google Scholar
  • 23 International Commission on Radiological Protection (ICRP) . Individual monitoring for internal exposure of workers. Replacement of ICRP Publication 54. ICRP Publication 78. Oxford: Pergamon Press; 1997
    Google Scholar
  • 24 Darrouzet E, Lindenthal S, Marcellin D. et al. The sodium/iodide symporter: State of the art of its molecular characterization. Biochimica and Biophysica Acta 2014; 1838: 244-253
    CrossrefPubMedGoogle Scholar
  • 25 Chou TC, Talaly P. A simple generalized equation for the analysis of multiple inhibitions of Michaelis–Menten kinetic systems. J Biol Chem 1977; 252: 6438-6442
    CrossrefPubMedGoogle Scholar
  • 26 Schäuble S, Stavrum AK, Puntervoll P. et al. Effect of substrate competition in kinetic models of metabolic networks. FEBS Letters 2013; 587: 2818-2824
    CrossrefPubMedGoogle Scholar
  • 27 Ramsden D, Passant FH, Peabody CO. et al. Radioiodine uptakes in the thyroid studies of the blocking and subsequent recovery of the gland following the administration of stable iodine. Health Phys 1967; 13: 633-646
    CrossrefPubMedGoogle Scholar
  • 28 Wootton R, Hammond BJ. A computer simulation study of optimal thyroid radiation protection during investigations involving the administration of radioiodine-labelled pharmaceuticals. Br J Radiol 1978; 51: 265-272
    CrossrefPubMedGoogle Scholar
  • 29 Blum M, Eisenbud M. Reduction of thyroid irradiation from I-131 by potassium iodide. JAMA 1967; 200: 1036-1040
    CrossrefPubMedGoogle Scholar
  • 30 Marinelli L, Quimby E, Hine G. Dosage determination with radioactive isotopes: II. Practical considerations in therapy and protection. Am J Roentgenol Radium Ther Nucl Med 1948; 59: 260-280
    PubMedGoogle Scholar
  • 31 Hine G, Brownell G. Radiation Dosimetry.. New York: Academic Press; 1956
    Google Scholar
  • 32 Stabin M. Nuclear medicine dosimetry. Phys Med Biol 2006; 51: R187-R202
    CrossrefPubMedGoogle Scholar
  • 33 Spetz J. Biodistribution of free 125I, 131I and 211At in rats. Master of Science thesis. Department of Radiation Physics. University of Gothenburg; Sweden: 2010
    Google Scholar
  • 34 Birchall A, Puncher M, Marsh JW. et al. IMBA Professional Plus: A flexible approach to internal dosimetry. Radiat Prot Dosimetry 2007; 125: 194-197
    PubMedGoogle Scholar
  • 35 Johansson L, Leide-Svegborn S, Mattsson S. et al. Biokinetics of iodide in man: Refinement of current ICRP dosimetry models. Cancer Biother Radiopharm 2003; 18: 445-450
    PubMedGoogle Scholar
  • 36 Harvey RP, Hamby DM, Palmer TS. A modified ICRP 66 iodine gas uptake model and its parametric uncertainty. Health Phys 2004; 87: 490-506
    CrossrefPubMedGoogle Scholar
  • 37 Matsuda N, Kumagai A, Ohtsuru A. et al. Assessment of internal exposure doses in Fukushima by a whole body counter within one month after the nuclear power plant accident. Radiat Res 2013; 179: 663-668
    CrossrefPubMedGoogle Scholar
  • 38 Strahlenschutzkommission (SSK) . Radiation protection principles for radioiodine therapy. Recommendation by the German Commission on Radiological Protection. Adopted at the 142nd session of the Commission on Radiological Protection on 5/6 December, 1996. In Veröffentlichungen der Strahlenschutzkommission Band 40. Gustav Fischer Verlag; 1998
    Google Scholar
  • 39 Goldsmith SJ. Radioactive iodine therapy of differentiated thyroid carcinoma: Redesigning the Paradigm. Mol Imaging Radionucl Ther 2017; 26 (Suppl. 01) 74-79
    PubMedGoogle Scholar
  • 40 Rall JE, Robbins J, Lewallen CG. The thyroid. In Pincus G, Thimann KV, Astwood EB. eds. The hormones. Physiology, chemistry, and applications. New York London: Academic Press; 1964. P 159-440
    Google Scholar
  • 41 McConahey WM, Keating Jr. FR, Power MH. An estimation of the renal and extrarenal clearance of radioiodine in man. J Clin Invest 1951; 30: 778-780
    CrossrefPubMedGoogle Scholar
  • 42 Stanley MM. The direct estimation of the rate of thyroid hormone formation in man; the effect of the iodide ion on thyroid iodine utilization. J Clin Endocrinol Metab 1949; 9: 941-954
    CrossrefPubMedGoogle Scholar
  • 43 Hänscheid H, Reiners C, Goulko G. et al. Facing the nuclear threat: Thyroid blocking revisited. J Clin Endocrinol Metab 2011; 96: 3511-3516
    CrossrefPubMedGoogle Scholar
  • 44 Orgiazzi J. L’iode stable et la prévention des expositions a l’iode radioactif. Energies-Santé 1996; 7: 379-385
    PubMedGoogle Scholar
  • 45 Wolff J. Iodide goiter and the pharmacologic effects of excess iodide. Am J Med 1969; 47: 101-124
    CrossrefPubMedGoogle Scholar
  • 46 Ericson LE, Nilsson M. Structural and functional aspects of the thyroid follicular epithelium. Toxicol Lett 1992; 64/65: 365-373
    CrossrefPubMedGoogle Scholar
  • 47 Simchowitz L. Interactions of bromide, iodide, and fluoride with the pathways of chloride transport and diffusion in human neutrophils. J Gen Physiol 1988; 91: 835-860
    CrossrefPubMedGoogle Scholar
  • 48 Fong P. Thyroid iodide efflux: a team effort?. J Physiol 2011; 589 (Pt24) 5929-5939
    CrossrefPubMedGoogle Scholar
  • 49 Hays MT. Kinetics of the human thyroid trap: Effects of iodide, thyrotropin, and propylthiouracil. J Nucl Med 1979; 20: 944-949
    PubMedGoogle Scholar
  • 50 Bazin JP, Fragu P, Di Paola R. et al. Tubiana. Early kinetics of thyroid trap in normal human patients and in thyroid disease. Eur J Nucl Med 1981; 6: 317-326
    PubMedGoogle Scholar
  • 51 Merrill EA, Clewell RA, Robinson PJ. et al. PBPK model for radioactive iodide and perchlorate kinetics and perchlorate-induced inhibition of iodide uptake in humans. Toxicol Sci 2005; 83: 25-43
    PubMedGoogle Scholar
  • 52 DeGroot LJ, Decostre P, Phair R. A mathematical model of human iodine metabolism. J of Clin Endocrinol & Metab 1971; 32: 757-765
    PubMedGoogle Scholar
  • 53 Matsunaga T, Kobayashi K. Sensitivity analysis on the deposition of inhaled radioactive iodine and the effectiveness of iodine prophylaxis. Jpn J Health Phys 2001; 36: 31-44
    CrossrefPubMedGoogle Scholar
  • 54 Eng PH, Cardona GR, Fang SL. et al. Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. Endocrinology 1999; 140: 3404-3410
    CrossrefPubMedGoogle Scholar
  • 55 Chung HR. Iodine and thyroid function. Ann Pediatr Endocrinol Metab 2014; 19: 8-12
    CrossrefPubMedGoogle Scholar
  • 56 Bürgi H. Iodine excess. Best Pract Res Clin Endocrinol Metab 2010; 24: 107-115
    CrossrefPubMedGoogle Scholar
  • 57 Koutras D, Livadas D. The minimum dose of potassium iodide which inhibits the thyroidal radioiodine uptake. Nucl Med 1966; 5: 256-261
    PubMedGoogle Scholar
  • 58 Sternthal E, Lipworth L, Stanley B. et al. Suppression of thyroid radioiodine uptake by various doses of stable iodide. N Engl J Med 1980; 303: 1083-1088
    CrossrefPubMedGoogle Scholar
  • 59 Plummer HS. The value of iodine in exopthalmic goiter. J Iowa Med Soc 1924; 14: 66-73
    PubMedGoogle Scholar
  • 60 Okamura K, Sato K, Fujikawa M. et al. Remission after potassium iodide therapy in patients with Graves hyperthyroidism exhibiting thionamide-associated side effects. J Clin Endocrinol Metab 2014; 99: 3995-4002
    CrossrefPubMedGoogle Scholar
  • 61 Calissendorff J, Falhammar H. Lugol’s solution and other iodide preparations: Perspectives and research directions in Graves disease. Endocrine 2017; 58: 467-473
    CrossrefPubMedGoogle Scholar
  • 62 Delange F. Administration of iodized oil during pregnancy: A summary of the published evidence. Bull WHO 1996; 74: 101-108
    PubMedGoogle Scholar
  • 63 Finkelstein R, Jacobi M. Fatal iodine poisoning: A clinico-pathologic and experimental study. Adv Intern Med 1937; 60: 1283-1296
    PubMedGoogle Scholar
  • 64 Tresch DD, Sweet DL, Keelan MHJ. Acute iodide intoxication with cardiac irritability. Arch Intern Med 1974; 134: 760-762
    CrossrefPubMedGoogle Scholar
  • 65 Georgitis WJ, McDermott MT, Kidd GS. An iodine load from water-purification tablets alters thyroid function in humans. Mil Med 1993; 158: 794-797
    CrossrefPubMedGoogle Scholar
  • 66 Leggett R. An age-specific biokinetic model for iodine. J Radiol Prot 2017; 37: 864-882
    CrossrefPubMedGoogle Scholar
  • 67 Berkovski V. New iodine models family for simulation of short-term biokinetic processes, pregnancy and lactation. Food Nutrition Bulletin. 2002; 23(3, supplement) 87-94
    PubMedGoogle Scholar
  • 68 Sun XF, Yang XF. Developmental effects of toxic doses of iodine. In Preedy VR, Burrow GN, Watson R. eds. Comprehensive handbook of iodine: Nutritional, biochemical, pathological and therapeutic aspects. Amsterdam Boston Heidelberg London Oxford New York Paris San Diego San Francisco Singapore Sidney Tokyo: Academic Press, Elsevier; 2009. P 855-864
    Google Scholar
  • 69 Connelly KJ, Boston BA, Pearce EN. et al. Congenital hypothyroidism caused by excess prenatal maternal iodine ingestion. J Pediatr 2012; 161: 760-762
    CrossrefPubMedGoogle Scholar
  • 70 Girling JC. Thyroid disorders in pregnancy. Cur Obstetrics & Gynaecol 2003; 13: 45-51
    PubMedGoogle Scholar
  • 71 Nauman J, Wolff J. Iodide prophylaxis in Poland after the Chernobyl reactor accident: benefits and risks. Am J Med 1993; 94: 524-532
    CrossrefPubMedGoogle Scholar