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Belugin K. V., Ozerskaya A. V., Chanchikova N. G. et al.
Aptamer-based radiopharmaceutical for PET/CT detection of lung cancer
© BELUGIN K. V., OZERSKAYA A. V., CHANCHIKOVA N. G., TOKAREV N. A., VOLZHENTSEV A. A., BADMAEV O. N., VEPRINTSEV D. V. UDC 54.057
DOI: 10.20333/25000136-2022-5-106
Aptamer-based radiopharmaceutical for PET/CT detection of lung cancer
K. V. Belugin1, A. V. Ozerskaya1,2, N. G. Chanchikova1, N. A. Tokarev1, A. A. Volzhentsev1, O. N. Badmaev1, D. V. Veprintsev3
'Federal Siberian Scientific and Clinical Center of the Federal Medical and Biological Agency, Krasnoyarsk 660037, Russian Federation 2Tomsk Polytechnic University, Tomsk 634050, Russian Federation
3Laboratory for Digital Controlled Drugs and Theranostics, Federal Research Center «Krasnoyarsk Science Center SB RAS», Krasnoyarsk 660036, Russian Federation
Abstract. The paper describes a new radiopharmaceutical for diagnosis of lung cancer obtained on the basis of a radiolabeled UC oligonucleotide and the study of its effectiveness in-vivo. As a result of the synthesis, an aptamer to lung cancer containing UC in the 3'-position was obtained and remained stable for 60 minutes. Prior to xenotransplantation of human lung cancer cells, the mice were immunosuppressed. Tumour volumes and locations were monitored using PET/CT. The study of accumulation of the radiopharmaceutical in the organs of mice in vivo has shown that the uC-labeled lung cancer aptamer specifically binds to lung cancer cells. A radiopharmaceutical based on uC-labeled LC aptamer against lung cancer is a promising drug for lung cancer diagnosing. Key words: radionuclide, lung cancer, aptamer, PET/CT.
Conflict of interest. The authors declare the absence of obvious and potential conflicts of interest associated with the publication of this article.
Citation: Belugin KV, Ozerskaya AV, Chanchikova NG, Tokarev NA, Volzhentsev AA, Badmaev ON, Veprintsev DV. Aptamer-based radiopharmaceutical for PET/CT detection of lung cancer. Siberian Medical Review. 2022;(5):106. DOI: 10.20333/25000136-2022-5-106
Introduction
One of the most sensitive diagnostic methods is positron emission tomography with computed tomography (PET-CT) using radionuclides [1]. 18F-fluorodeoxyglucose, "C-methionine, nC-choline and other radionuclides are used to detect malignant neoplasms, determine the stage and extent of the tumour process [2]. However, despite the high sensitivity of the method, the radiopharmaceuticals themselves do not show high specificity since they can accumulate not only in the malignant tumours, but also in all organs and tissues with high metabolic activity [1]. An alternative to this radiopharmaceutical is a drug based on the nC aptamer [3]. The paper describes a new radiopharmaceutical for the diagnosis of lung cancer, obtained on the basis of a radiolabeled nC oligonucleotide and the study of its effectiveness in vivo.
Material and methods
The introduction of nC into the lung cancer aptamer was carried out in a dipolar aprotic solvent, which well supports DMSO 2nd order nucleophilic reactions. Synthesis of the product is carried out in the "Synthra MeI-Plus" module (Synthra, Germany), which makes it possible to obtain nC-CH3I methyl iodide from carbon dioxide nC-CO2 produced in a cyclotron and delivered to the synthesis module in the target gas stream. The synthesis includes the step of labelling with nC the targeting molecule - the thiolated DNA-aptamer.
The mice were immunosuppressed prior to xenotransplantation of human lung cancer cells. The tumour in the lungs of the mice developed within 2 weeks.
Results and discussion
As a result of the synthesis, an aptamer to lung cancer containing 11C in the 3'-position was obtained that remained stable for 60 minutes. The efficiency of the binding of the 3'-nC-LC aptamer complex to cancer cells in vivo was assessed in ICR mice with a transplanted human lung tumour using PET/CT. The ability of the nC radionuclide (LC 3'-nC aptamer) to find and identify tumour foci and metastases in the body was assessed using immunosuppressed ICR mice transplanted with a primary culture of lung cancer into the right lung. The study of the accumulation of the radiopharmaceutical in the organs ofmice in
Figure. Lung tumour lesion detected by PET/CT using "C-labeled lung cancer aptamer.
106 Siberian Medical
vivo showed that the nC-labeled lung cancer aptamer specifically binds to lung cancer cells (see the Figure).
Conclusion
A radiopharmaceutical based on nC-labeled LC aptamer against lung cancer is a promising drug for lung cancer diagnostics.
Synthesis of 11C-aptamer and PET/CT visualization was funded by the Federal Medical Biological Agency; project 1220418001322 (K.VB). Aptamer modeling was funded by the Ministry of Science and Higher Education of the Russian Federation; project FWES-2022-0005 (A.S.K.)
References
1. Khalid U, Vi C, Henri J, Macdonald J, Eu P, Mandarano G, Shigdar S. Radiolabelled Aptamers for Theranostic Treatment of Cancer. Pharmaceuticals. 2019;12(2). D0I:10.3390/ph12010002
2. Bollineni V, Kramer G, Jansma E, Liu Y, Oyen W. A systematic review on [18F] FLT-PET uptake as a measure of treatment response in cancer patients. European Journal of Cancer. 2016;(55): 81-97.
3. Ozerskaya AV, Zamay TN, Kolovskaya OS, Tokarev NA, Belugin KV, Chanchikova NG, Badmaev ON, Zamay GS, Shchugoreva IA, Moryachkov RV, Zabluda VN, Khorzhevskii VA, Shepelevich NV, Gap-poev SV, Karlova EA, Saveleva AS, Volzhentsev AA, Blagodatova AN, Lukyanenko KA, Veprintsev DV, Smolyarova TE, Tomilin FN, Zamay SS, Silnikov VN, Berezovski MV, Kichkailo AS. "C-Radiolabeled Aptamer for Imaging of Tumor and Metastasis Using Positron Emission Tomography - Computed Tomography. Molecular Therapy - Nucleic Acids. 2021;(26):1159-1172.
Author information
Kirill V. Belugin, radiochemist, Federal Siberian Scientific and Clinical Center of the Federal Medical and Biological Agency; Address: 26, Kolomenskaya Str., Krasnoyarsk Russian Federation 660037; Phone: +79138314969, e-mail: [email protected]
Anastasia V. Ozerskay, head of quality control department, Tomsk Polytechnic University; Address: 30, Lenin Str., Tomsk, Russian Federatio, 634050; Federal Siberian Scientific and Clinical Center of the Federal Medical and Biological Agency; Address: 26, Kolomenskaya Str., Krasnoyarsk, Russian Federation 660037; Phone: +7(391)2743100, e-mail: ozerskaya_av@ skc-fmba.ru
Natalia G. Chanchikova, Director, Federal Siberian Scientific and Clinical Center of the Federal Medical and Biological Agency; Address: 26, Kolomenskaya Str., Krasnoyarsk, Russian Federation 660037; Phone: +7(391)2743100, e-mail [email protected]
Nikolay A. Tokarev, Federal Siberian Scientific and Clinical Center of the Federal Medical and Biological Agency; Address: 26, Kolomenskaya Str., Krasnoyarsk, Russian Federation 660037; Phone: +7(391)2743100, e-mail [email protected]
Aleksander A. Volzhentsev, radiochemist, Federal Siberian Scientific and Clinical Center of the Federal Medical and Biological Agency; Address: 26, Kolomenskaya Str., Krasnoyarsk, Russian Federation 660037; Phone: +7(391)2743100
Oleg N. Badmaev, radiochemist, Federal Siberian Scientific and Clinical Center of the Federal Medical and Biological Agency; Address: 26, Kolomenskaya Str., Krasnoyarsk Russian Federation 660037; Phone: +79235731093, e-mail: [email protected]
Dmitry V. Veprintsev, Cand. Phis.-Math. Sci., Senior Researcher, Krasnoyarsk Scientific Center of the SB RAS; Address: 50, Akademgorodok, Krasnoyarsk, Russian Federation 660036; Phone:+7(391)2907988; e-mail: [email protected]
Received 17 June 2022 Revision Received 20 August 2022 Accepted 30 August 2022
Review. 2022;(5):106
