Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Visualization of Glioblastoma with Infrared-Labeled Aptamers for Fluorescent Guided Surgery

Version 1 : Received: 11 December 2023 / Approved: 15 December 2023 / Online: 15 December 2023 (06:01:00 CET)

How to cite: Zamay, G.S.; Koshmanova, A.A.; Narodov, A.A.; Gorbushin, A.K.; Voronkovskiy, I.I.; Grek, D.S.; Luzan, N.A.; Nikolaeva, E.D.; Kolovskaya, O.S.; Shchugoreva, I.A.; Artyushenko, P.V.; Glazyrin, Y.E.; Fedotovskaya, V.D.; Veprintcev, D.V.; Belugin, K.V.; Lukyanenko, K.A.; Kirichenko, A.K.; Lapin, I.N.; Khorzhevskii, V.A.; Semichev, E.V.; Mohov, A.A.; Kirichenko, D.A.; Tokarev, N.A.; Chanchikova, N.G.; Krat, A.V.; Zukov, R.A.; Bakhtina, V.I.; Shnyakin, P.G.; Shesternya, P.A.; Tomilin, F.N.; Kosinova, A.A.; Svetlichnyi, V.A.; Zamay, T.N.; Mezko, V.S.; Berezovski, M.V.; Kichkailo, A.S. Visualization of Glioblastoma with Infrared-Labeled Aptamers for Fluorescent Guided Surgery. Preprints 2023, 2023121146. https://doi.org/10.20944/preprints202312.1146.v1 Zamay, G.S.; Koshmanova, A.A.; Narodov, A.A.; Gorbushin, A.K.; Voronkovskiy, I.I.; Grek, D.S.; Luzan, N.A.; Nikolaeva, E.D.; Kolovskaya, O.S.; Shchugoreva, I.A.; Artyushenko, P.V.; Glazyrin, Y.E.; Fedotovskaya, V.D.; Veprintcev, D.V.; Belugin, K.V.; Lukyanenko, K.A.; Kirichenko, A.K.; Lapin, I.N.; Khorzhevskii, V.A.; Semichev, E.V.; Mohov, A.A.; Kirichenko, D.A.; Tokarev, N.A.; Chanchikova, N.G.; Krat, A.V.; Zukov, R.A.; Bakhtina, V.I.; Shnyakin, P.G.; Shesternya, P.A.; Tomilin, F.N.; Kosinova, A.A.; Svetlichnyi, V.A.; Zamay, T.N.; Mezko, V.S.; Berezovski, M.V.; Kichkailo, A.S. Visualization of Glioblastoma with Infrared-Labeled Aptamers for Fluorescent Guided Surgery. Preprints 2023, 2023121146. https://doi.org/10.20944/preprints202312.1146.v1

Abstract

Background: Glioblastoma remains a challenging brain tumor to treat due to its infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful tumor resection. This study introduces an innovative intraoperative visualization method utilizing a surgical fluorescence microscope to precisely locate tumor cells. The focus of the study is on IR-Glint, a novel preparation comprising Cy7.5-labeled aptamers Gli-233nt and Gli-55_3L specific to human glioblastoma. Methods: The aptamers were modified using molecular modeling and quantum chemical techniques. The effectiveness of the preparation was assessed using flow cytometry and microscopy on primary cultures of human glioblastoma. In vivo studies were conducted on mouse and rabbit models, employing orthotopic xenotransplantation of human brain glioblastoma with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. Results: The experiments validated the potential of IR-Glint for intraoperative visualization of glioblastoma using infrared imaging. Surface application of the aptamer-based formulation on the brain allowed clear visualization of the tumor, aiding surgeons in tumor resection. This approach also reduces the dosage required and mitigates potential toxic effects on the patient. Conclusions: This study demonstrates the promising potential of using in-frared dye-labeled aptamers for intraoperative visualization of glioblastoma. By improving surgical treatment outcomes in neurosurgery, this novel approach may pave the way for future advancements in the field.

Keywords

glial brain tumor; astrocytoma; fluorescence guided surgery; infrared dye; tumor imaging in vivo; DNA-aptamers; aptamer spatial structure; molecular modeling

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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