A.V. Matveev¹

1 Dostoevsky Omsk State University (Omsk, Russia)

In Russian nuclear medicine (IDP) individual dosimetric planning of radioiodine therapy is increasingly used, in which the therapeutic activity of radioiodine is introduced into patient's body, calculated on the basis of its individual pharmacokinetics by the value of the absorbed dose which must be implemented in the thyroid gland. However this method requires significant economic costs, the availability of highly qualified engineering and technical personnel in the medical organization and the use of special diagnostic equipment, which still does not allow it to be implemented in many regions of our country. In addition, there are practically no full-fledged recommendations on IDP in Russian publications, and a number of significant problems related to it remain unresolved, including those based on the use of compartmental modeling of radioiodine kinetics.

Aim of work – generalize the previously developed four-compartment model of radioiodine kinetics during its oral administration to a five-compartment model with the allocation of a kidney compartment and a urinary bladder compartment with the possibility of calculating the radiation load on the bladder, taking into account its periodic emptying. To apply the five-compartment model for IDP of radioiodine therapy.

The work is based on the principles and methods of pharmacokinetics of radiopharmaceuticals (compartmental modeling). The HookJeeves method was used to find the minimum of the residual functional when identifying the values of the transport constants of the model. The calculation of dosimetric characteristics and therapeutic activity is based on the method of calculating absorbed doses using the compartment radioiodine activity functions found in the simulation process. To identify the model parameters, we used the results of radiometry of the thyroid gland and urine of five patients with radioiodine injected into the body.

A five-compartment model of radioiodine kinetics during its oral intake has been developed. For five patients with Graves' disease the transport constants of the model were identified and individual pharmacokinetic and dosimetric characteristics were calculated (halflife periods, maximum thyroid activity and time to reach it, absorbed doses to critical organs and tissues, and therapeutic activity administered). The time activity relationships for all compartments of the model are obtained and analyzed. The stunning-effect was evaluated for one patient.

With individual dosimetric planning, there are no cases of under- or over-irradiation of thyroid tissue, and dose loads on critical organs and tissues are tolerant. At the same time the values of the administered therapeutic activity vary widely, so for each patient it should be strictly individual and calculated based on modeling.

Matveev A.V. Compartmental models of radioiodine kinetics in individual dosimetric planning of Graves disease therapy. Technologies of living systems. 2021. V. 18. № 1. P. 41–50. DOI: 10.18127/j20700997-202101-04 (In Russian).

1. Fard-Esfahani P., Beiki D., Fallahi B., Fard-Esfahani A., Emami-Ardekani A., Ansari M., Eftekhari M. Radioiodine therapy for hyperthyroidism. Iranian Journal of Nuclear Medicine. 2011. V. 19. № 2. P. 1–12.
2. Cyb A.F., Dreval' A.V., Garbuzov P.I. Radiojodterapiya tireotoksikoza: rukovodstvo. M.: GEOTAR-Media. 2009. 160 s. (In Russian).
3. Solodkij V.A., Fomin D.K., Galushko D.A., Pestrickaya E.A. Vysokodoznaya radiojodterapiya bolezni Grejvsa. Vestnik Rossijskogo nauchnogo centra rentgenoradiologii Minzdrava Rossii. 2013. T. 4. № 13. S. 11–12 (In Russian).
4. Al-jubeh W., Shaheen A., Zalloum O. Radioiodine I-131 for Diagnosing and Treatment of Thyroid Diseases. Conference Paper. 2012. № 6. URL: https://www.researchgate.net/publication/295919808. 
5. Radhi H.T., Jamal H.F., Sarwani A.A., Jamal A.J., Al-Alawi M.F., Alsabea A.S., Al-Azman B.A., Alsaleh Z.J. Efficacy of a single fixed 131I dose of radioactive iodine for the treatment of hyperthyroidism. Clinical Investigation (London). 2019. V. 9. № 4. P. 111–120.
6. Lipanova N.N., Klepov A.N., Narkevich B.Ya. Dozimetricheskoe planirovanie i dozovyj kontrol' v radiojodoterapii raka shchitovidnoj zhelezy. Medicinskaya radiologiya i radiacionnaya bezopasnost'. 2012. T. 57. № 3. S. 53–65 (In Russian).
7. Bellman R. Matematicheskie metody v medicine: Per. s angl. A.P. Asachenkova, N.A. Shal'novoj / Pod red. L.N. Belyh. M.: Mir. 1987. 200 c. (In Russian).
8. Vlasova O.P., Klepov A.N., Matusevich E.S., Poculko E.P. Matematicheskoe modelirovanie dlya dozimetricheskogo planirovaniya radiojodterapii pacientov s zabolevaniyami shchitovidnoj zhelezy. Vestnik novyh medicinskih tekhnologij. 2008. T. 15. № 1. C. 17–19 (In Russian).
9. Lipanova N.N. Radiobiologicheskoe i dozimetricheskoe obosnovanie radionuklidnoj terapii zabolevanij shchitovidnoj zhelezy: Diss. ... kand. fiz.-mat. nauk. M. 2012. 115 s. (In Russian) (In Russian).
10. Vlasova O.P. Metod identifikacii parametrov metabolizma radiojoda i raschet pogloshchennyh doz pri radionuklidnoj terapii shchitovidnoj zhelezy: Diss. … kand. biol. nauk. M. 2010. 124 s. (In Russian).
11. Matveev A.V., Noskovec D.Yu. Farmakokineticheskoe modelirovanie i dozimetricheskoe planirovanie radiojodterapii tireotoksikoza. Vestnik Omskogo universiteta. 2014. № 4. C. 57–64 (In Russian).
12. Matveev A.V., Noskovec D.Yu. Osobennosti dozimetricheskogo planirovaniya radiojodterapii na osnove farmakokineticheskogo modelirovaniya. Vestnik Omskogo universiteta. 2016. № 3. C. 74–83 (In Russian).
13. Svidetel'stvo o registracii programmy dlya EVM RU 2016616640. Kompleks farmakokineticheskogo modelirovaniya i rascheta pogloshchennyh doz pri radiojodterapii bolezni Grejvsa / A.V. Matveev, D.Yu. Noskovec (In Russian).
14. Lizogub D.S., Matveev A.V. Radioizotopnye metody issledovaniya v diagnostike zabolevanij shchitovidnoj zhelezy. Molodezh' tret'ego tysyacheletiya [Elektronnyj resurs]: Sb. nauchnyh statej / [otv. red. S. V. Belim]. Elektron. tekst. dan. Omsk: Izd-vo Om. gos. un-ta, 2017. 1 elektron. opt. disk (CD-ROM); 12 sm. URL: https://omsu.ru/science/materialy-konferentsiy/2017/M-III_2017.pdf (In Russian).
15. Sergienko V.I., Dzhelliff R., Bondareva I.B. Prikladnaya farmakokinetika: osnovnye polozheniya i klinicheskoe primenenie. M.: Izd-vo RAMN. 2003. 208 s. (In Russian).
16. Huk R., Dzhivs T.A. Pryamoj poisk resheniya dlya chislovyh i statisticheskih problem. M.: Mir. 1961. 219 s. (In Russian).
17. Kalitkin N.N., Koryakin P.V. Chislennye metody: v 2 kn. Kn. 2. Metody matematicheskoj fiziki. M.: Izd. centr «Akademiya». 2013. 304 s. (In Russian).
18. Galanin M.P., Hodzhaeva S.R. Razrabotka i testirovanie metodov resheniya zhestkih obyknovennyh differencial'nyh uravnenij. Matematicheskoe modelirovanie i chislennye metody. 2014. № 4. S. 95–119 (In Russian).
19. Mazzaglia S., Stella G., Barone Tonghi L., Tuvé C.N., Politi G., Pellegriti G., Gueli A.M. Absorbed dose evaluation in radioiodine therapy with different approaches. Instruments. 2019. V. 3. № 3. URL: https://www.mdpi.com/2410-390X/3/3/39.
20. Sisson J.C., Avram A.M., Lawson S.A., Gauger P.G., Doherty G.M. The so-called stunning of thyroid tissue. Journal of Nuclear Medicine. 2006. V. 47. № 9. P. 1406–1412.
21. Gerard S.K., Park H.M. Authors of the letter and the reply – 131I dosimetry and thyroid stunning. Journal of Nuclear Medicine. 2003.  V. 44. № 12. P. 2039–2040.
22. Lassmann M., Luster M., Hänscheid H., Reiners C. Impact of 131I diagnostic activities on the biokinetics of thyroid remnants. Journal of Nuclear Medicine. 2004. V. 45. № 4. P. 619–625.
23. Sheremeta M.S., Degtyarev M.V., Rumyancev P.O. Radiojodterapiya aktivnost'yu 550 MBk I-131 bol'nyh tireotoksikozom. Endokrinnaya hirurgiya. 2016. T. 10. № 2. S. 5–9 (In Russian).