Abstract

The radioiodine therapy is the most well-known branch of radionuclide therapy. The therapy composed of thyroidectomy and iodine-131 radiopharmaceutical is the “gold standard” for treatment of differentiated thyroid cancer patients (DTC). Given metastases in lymph nodes such therapy is ab-solutely exclusive treatment mode. At the same time, despite the targeted effect of radioiodine on pathological foci a side internal exposure of healthy organs and tissues is noted in the course of radioiodine therapy. Therefore, a reliable assessment of the side exposure is necessary taking into account the individual characteristics of patients considering that the side dose varies significantly from patient to patient. For this reason, the identification of significance of personal clinic-diagnostic factors determined the side whole body exposure is the vital and important task. In this aspect, the cytogenetic examination of DTC patients by means of the analysis of chromosomal aberrations in peripheral blood lymphocytes is the goal of essential importance. The certain types of chromosomal aberrations are specific radiation markers that unequivocally indicate radiation exposure. Using the frequency of radiation markers the side absorbed dose can be reliably estimated. In the present work, the statistical analysis of the significance of various clinic-diagnostic factors in relation to the induction of radiation markers in the blood lymphocytes was performed. For that end the results of the cytoge-netic examination of the group comprised of 38 DTC patients have been used. The examined patients underwent a course of radioiodine therapy in the department of radionuclide therapy of the A.F. Tsyb MRRC, Obninsk. The slide preparation and cytogenetic analysis were carried out in the laboratory of radiation cytogenetic of the same Center. The performed analysis of the correlation matrix with respect to the dependence of the increased frequency of stable and unstable markers resulted from a onetime course of radioiodine therapy showed no meaningfulness at the level R>0.3 for all the studied factors. For the absolute value of the frequency of radiation markers, both before and after radioiodine therapy, the meaningful relationship was found at the level R>0.7 for unstable and at the level R>0.8 for stable markers with a total administered activity of radioiodine during all the previous courses of radioiodine therapy.

Key words
nuclear medicine, thyroid cancer, radiopharmaceuticals, radioiodine therapy, side exposure, radiation marker, cytogenetics, biodosimetry, chromosomal aberrations, blood lymphocytes.

References

1. Malignant neoplasms in Russia in 2018 (morbidity and mortality). Eds.: A.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow, Herzen MORI – branch of the NMRRC of the Ministry of Health of the Russian Federation, 2019. 250 p. (In Russian).

2. Krylov V.V., Garbuzov P.I., Kochetova T.Yu., Shurinov A.Yu., Borodavina E.V. Therapeutic radiology na-tional leadership. Chapter 34. Radionuclide therapy. Eds.: A.D. Kaprin, Yu.S. Mardynsky. Moscow, GEOTAR-Media, 2018, pp. 637-665. (In Russian).

3. Silberstein E.B. Radioiodine: the classic theranostic agent. Semin. Nucl. Med., 2012, vol. 42, no. 3. pp. 164-170.

4. Khvostunov I.K., Saenko V.A., Krylov V.V., Rodichev A.A., Yamashita S. Cytogenetic biodosimetry and dose-rate effect after radioiodine therapy for thyroid cancer. Radiat. Environ. Biophys., 2017, vol. 56, no. 3, pp. 213-226.

5. Khvostunov I.K., Krylov V.V., Rodichev A.A., Shepel N.N., Korovchuk O.N., Pyatenko V.S., Khvostunova T.I. The dose of total radiation in the treatment of differentiated thyroid cancer with radioactive iodine. Radiatsonnaya biologiya. Radioekologiya – Radiation Biology. Radioecology, 2017, vol. 57, no. 5, pp. 471-485. (In Russian).

6. Robbins R.J., Schlumberger M.J. The evolving role of 131-I for the treatment of differentiated thyroid carcinoma. J. Nucl. Med., 2005, vol. 46, no. 1, pp. 28S-37S.

7. Khvostunov I.K., Krylov V.V., Rodichev A.A., Shepel N.N., Korovchuk O.N., Kochetova T.Yu., Pyatenko V.S., Khvostunova T.I. Assessment of the adverse radiation effect of radioiodine therapy for children and adolescents based on cytogenetic examination. Dostizheniya i perspektivy` detskoj onkologii – Achievements and prospects of pediatric oncology, Abstracts of the VII Congress of Pediatric Oncologists of Russia with international participation, Moscow, October 25-26, 2018. Onkopediatriya – Oncopediatrics, 2018, vol. 5, no. 3 (Supplement), pp. 15. (In Russian).

8. Brill A.B., Stabin M., Bouville A., Ron E. Normal organ radiation dosimetry and associated uncertainties in nuclear medicine, with emphasis on Iodine-131. Radiat. Res., 2006, vol. 166, no. 1, pp. 128-140.

9. Van Nostrand D. The benefits and risks of I-131 therapy in patients with well-differentiated thyroid cancer. Thyroid, 2009, vol. 19, no. 12. pp. 1381-1391.

10. Kulkarni K., Van Nostrand D., Atkins F., Aiken M., Burman K., Wartofsky L. The frequency with which empiric amounts of radioiodine “over-“ or “under-“ treat patients with metastatic well-differentiated thyroid cancer. Thyroid, 2006, vol. 16, no. 1, pp. 1-5.

11. Stabin M.G., Sharkey R.M., Siegel J.A. RADAR commentary: evolution and current status of dosimetry in nuclear medicine. J. Nucl. Med., 2011, vol. 52, no. 7, pp. 1156-1161.

12. Verburg F.A., Lassmann M., Mäder U., Luster M., Reiners C., Hänschei H. The absorbed dose to the blood is a better predictor of ablation success than the administered 131-I activity in thyroid cancer patients. Eur. J. Nucl. Med. Mol. Imaging, 2011, vol. 38, no. 4, pp. 673-680.

13. Benua R.S., Leeper R.D. A method and rationale for treating thyroid carcinoma with the largest safe dose of I-131. Frontiers of Thyroidology. Еds.: G.A. Meideros-Neto, E. Gaitan. V. II. New York, Plenum, 1986, pp. 1317-1321.

14. De Keizer B., Hoekstra A., Konijnenberg M.W. Bone marrow dosimetry and safety of high ¹³¹I activities given after recombinant human thyroid-stimulating hormone to treat metastatic differentiated thyroid cancer. J. Nucl. Med., 2004, vol. 45, no. 9, pp. 1549-1554.

15. Kalistratova V.S., Belyaev I.K., Zhorova E.S., Nisimov P.G., Parfenova I.M., Tishchenko G.S., Tsapkov M.M. Radiobiology of incorporated radionuclides. Ed.: V.S. Kalistratova. Moscow, A.I. Burnazyan FMBC FMBA of Russia, 2012. 464 p. (In Russian).

16. Willegaignon J., Malvestiti L.F., Guimarães M.I.C., Sapienza M.T., Endo I.S., Neto G.C., Marone M., Sordi G.-M.A.A. 131-I effective half-life (Teff) for patients with thyroid cancer. Health Phys., 2006, vol. 91, no. 2, pp. 119-122.

17. Cytogenetic analysis for radiation dose assessment: a manual. Technical Reports Series IAEA N 405. Vienna, IAEA, 2001. 127 p.

18. Herate C., Sabatier L. Retrospective biodosimetry techniques: focus on cytogenetics assays for individuals exposed to ionizing radiation. Mutat. Res., 2020, vol. 783, pp. 108287. DOI: 10.1016/j.mrrev.2019.108287.

Full-text article (in Russian)