Ulyanovsk Medico-biological Journal

Физиология

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https://doi.org/10.23648/UMBJ.2017.26.6228

УДК 57.044+611.018

 

ИЗУЧЕНИЕ ХАРАКТЕРА РАСПРЕДЕЛЕНИЯ СОЛЕЙ ЛЮТЕЦИЯ И ИЗМЕНЕНИЙ В ОРГАНАХ И ТКАНЯХ КРЫС ПОСЛЕ ИХ ВВЕДЕНИЯ

Д.А. Масленникова, С.М. Слесарев, Е.В. Слесарева, А.И. Харин, О.В. Столбовская, А.В. Хохлова, Е.С. Погодина, Д.А. Зажома, С.Н. Ворсина, Ю.В. Саенко

ФГБОУ ВО «Ульяновский государственный университет», г. Ульяновск, Россия

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В современной практике лечения онкологических заболеваний наибольшей эффективностью обладает сочетание нескольких методик. При этом лучший результат в терапии рака достигается при использовании лучевой терапии, особенно в сочетании с таргетными методами. В радионуклидной терапии многих видов рака широко применяется изотоп лютеция-177. В связи с этим представляется актуальным определить, каким образом данный элемент распределяется в различных органах и тканях организма.

Цель. Изучить закономерности распределения хлорида лютеция в тканях и органах белых крыс при различных способах введения.

Материалы и методы. Объектами исследования являлись органы и ткани белых крыс. Распределение солей лютеция в органах и тканях определялось методом атомно-эмиссионного спектрального анализа. Морфологическое исследование проводилось по стандартной гистологической методике.

Результаты. Исследование показало, что лютеций накапливается главным образом в тканях печени, поджелудочной железы, селезенки, тонкой кишки, тимуса и лимфатических узлах. Незначительное количество лютеция было обнаружено в легких, сердце, почках, семенниках, грудине, головном мозге, коже и крови крыс. Гистологический анализ тканей выявил явления хронического воспаления в органах иммунной системы и компенсаторно-приспособительные процессы в печени. При этом в органах, не имеющих непосредственной связи с иммунной системой, патологических изменений после введения лютеция не наблюдалось.

Заключение. Выявленные закономерности распределения нерадиоактивного лютеция в органах и тканях белых крыс частично могут быть использованы для разработки методов лечения онкологических заболеваний лимфатической системы и печени.

Ключевые слова: хлорид лютеция, лантаноиды, распределение лютеция.

 

Литература

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LUTETIUM BIODISTRIBUTION IN RAT ORGAN AND TISSUE AND CONSECUTIVE CHANGES AFTER LUTETIUM SALT INJECTION

D.A. Maslennikova, S.M. Slesarev, E.V. Slesareva, A.I. Kharin, O.V. Stolbovskaya, A.V. Khokhlova, E.S. Pogodina, D.A. Zazhoma, S.N. Vorsina, Yu.V. Saenko

Ulyanovsk State University, Ulyanovsk, Russia

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In modern cancer treatment practices, combination of different methods is the most effective strategy. The best result in cancer therapy is reported to be after radionuclide therapy, especially in combination with target methods. Lutetium-177 is widely used for radionuclide therapy of different cancers. Thus, it seems relevant to determine how this element distributes in various tissues and organs.

The objective of the study is to examine lutetium chloride pattern in white rat organs and tissues after different injection methods.

Materials and Methods. The objects of the study were organs and tissues of white rats. Lutetium salt biodistribution in organs and tissues was determined by the method of atomic emission spectroscopy. Morphological examination was carried out according to a standard histological technique.

Results. The study showed that lutetium accumulated mainly in the tissues of a liver, pancreas, spleen, small intestine, thymus and lymph node. A small amount of lutetium was found in the lungs, heart, kidneys, testis, sternum, brain, skin and blood of rats. Histological tissue analysis revealed chronic inflammation of the immune system and compensatory-adaptive processes in the liver. It is worth noting that there were no pathological changes in organs, which did not belong to the immune system after lutetium injections.

Conclusion. Revealed pattern of non-radioactive lutetium biodistribution in white rat organs and tissues could be partially used in development of methods for treating oncological diseases of the lymphatic system and liver.

Keywords: lutetium chloride, lanthanide, lutetium biodistribution.

 

References

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2.    Turner J.H. Treatment of painful skeletal metastases. Alasbimn Journal, Special Issue: 8th World Congress of Nuclear Medicine. 2002: 17.

3.    Enrique O., Zhongyun P., Parma E.P., Pusuwan P., Riccabona G., Tian J-H., Padhi A.K. Efficacy and toxicity of 153 Sm-EDTMP in the palliative treatment of painful bone metastases. World J. Nucl. Med. 2002; 1: 21–27.

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6.    Yoshikawa T., Naito Y. What is oxidative stress? Japan Med. Assoc. J. 2002; 45 (7): 271–276.

7.    Zukau V.V., Kabanov D.V. Osobennosti polucheniya radionuklida lyutetsiy-177 na reaktore IRT-T [Lutetium-177 radionuclide synthesis with IRT-T reactor]. Izotopy: tehnologii, materialy i primenenie: materialy Mezhdunarodnoj nauchnoj konferencii molodyh uchenyh, aspirantov i studentov [Isotopes: technologies, materials and applications: Proceedings of the International Scientific Conference for Young Scientists, Postgraduates and Students]. October 20-24, 2014. Tomsk; 2014: 76–77 (in Russian).

8.    Yook S., Cai Z., Lu Y., Winnik M.A., Pignol J.P., Reilly R.M. Radiation Nanomedicine for EGFR-Positive Breast Cancer: Panitumumab-Modified Gold Nanoparticles Complexed to the β-Particle-Emitter, 177Lu. Mol. Pharm. 2015; 12 (11): 3963–3972.

9.    Lindenblatt D., Fischer E., Cohrs S., Schibli R., Grunberg J. Paclitaxel improved anti-L1CAM lutetium-177 radioimmunotherapy in an ovarian cancer xenograft model. EJNMMI Res. 2014; 4 (1): 54.

10. Abbasi I.A. Studies on the Labeling of Ethylenediaminetetramethylene Phosphonic Acid, Methylene Diphosphonate, Sodium Pyrophosphate and Hydroxyapatite with Lutetium-177 for use in Nuclear Medicine. World J. Nucl. Med. 2015: 14 (2): 95–100.

11. Koppe M.J. Bleichrodt R.P., Soede A.C., Verhofstad A.A., Goldenberg D.M., Oyen W.J., Boerman O.C. Biodistribution and therapeutic efficacy of (125/131)I-, (186)Re-, (88/90)Y-, or (177)Lu-labeled monoclonal antibody MN-14 to carcinoembryonic antigen in mice with small peritoneal metastases of colorectal origin. J. Nucl. Med. 2004; 45 (7): 1224–1232.

12. Örbom A., Eriksson S.E., Eligström E., Ohlsson T., Nilsson R., Tennvall J., Strand S.E. The intratumoral distribution of radiolabeled 177Lu-BR96 monoclonal antibodies changes in relation to tumor histology over time in a syngeneic rat colon carcinoma model. J. Nucl. Med. 2013; 54 (8):
1404–1410.

13. Agarwal K.K., Singla S., Arora G., Bal C. (177)Lu-EDTMP for palliation of pain from bone metastases in patients with prostate and breast cancer: a phase II study. Eur. J. Nucl. Med. Mol. Imaging. 2015; 42 (1): 79–88.

14. Yuan J., Liu C., Liu X., Wang Y., Kuai D., Zhang G., Zaknun J.J. Efficacy and safety of 177Lu-EDTMP in bone metastatic pain palliation in breast cancer and hormone refractory prostate cancer: a phase II study. Clin. Nucl. Med. 2013; 38 (2): 88–92.

15. Kulkarni H.R., Prasad V., Schuchardt C., Baum R.P. Is there a correlation between peptide receptor radionuclide therapy-associated hematological toxicity and spleen dose? Recent Results Cancer Res. 2013; 194: 561–566.

16. Seidl C., Zöckler C., Beck R., Quintanilla-Martinez L., Bruchertseifer F., Senekowitsch-Schmidtke R. 177Lu-immunotherapy of experimental peritoneal carcinomatosis shows comparable effectiveness to 213Bi-immunotherapy, but causes toxicity not observed with 213Bi. Eur. J. Nucl. Med. Mol. Imaging. 2011; 38 (2): 312–322.

17. Andreeva O.S., Kiselev V.I., Malinina V.I. Redkozemel'nye elementy. Radiatsionno-gigienicheskie aspekty [Rare earth elements. Radiation and hygienic aspects]. Moscow: Atomizdat; 1975. 152 (in Russian).

18. Watanabe K. A comparison of the tissue distribution of colloidal lutecium-177 and gold-198 in rats after intraperitoneal and intratumoral injection. Experimental studies of radiocolloidal therapy. 1962; 21: 1147–1162.

19. Dufresne A., Krier G., Muller J.F., Case B., Perrault G. Lanthanide particles in the lung of a printer. Sci. Total Environ. 1994; 151: 249–252.

20. Hirano S., Suzuki K.T. Exposure, metabolism, and toxicity of rare earths and related compounds. Environ. Health Perspect. 1996; 104 (1): 85–95.

21. Thakral P., Singla S., Yadav M.P., Vasisht A., Sharma A., Gupta S.K., Bal C.S., Snehlata, Malhotra A. An approach for conjugation of 177Lu-DOTA-SCN-Rituximab (BioSim) & its evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins lymphoma patients. Indian J. Med. Res. 2014; 139 (4): 544–554.