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Fluorescence imaging analysis of distribution of indocyanine green in molecular and nanoform in tumor model
Institution:1. Prokhorov General Physics Institute of the Russian Academy of Science, Vavilova str.38, Moscow 119991, Russia;2. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Science, Miklukho-Maklaya str., 16/10, Moscow 117997, Russia;3. National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 2nd Botkin Ave. 3, Moscow 125284, Russia;4. Centre de Recherche en Automatique de Nancy, CNRS, Université de Lorraine, Campus Sciences Boulevard des Aiguillettes BP 70239 54506 Vandoeuvre Les Nancy Cedex, Vandoeuvre-lès-Nancy 54519, France;5. Institut de Cancérologie de Lorraine, 6 Av. de Bourgogne, Vandoeuvre-lès-Nancy 54519, France;6. National Research Nuclear University “MEPhI”, Kashirskoe shosse, 31, Moscow 115409, Russia;1. Gamaleya National Research Center of Epidemiology and Microbiology, Moscow, 123098 Russia;2. Prokhorov General Physics Institute of the Russian Academy of Sciences, Moscow, 119991 Russia;3. National Research Nuclear University “MEPhI”, Moscow, 115409 Russia;4. I.M. Sechenov First Moscow State Medical University, Moscow, 119992 Russia;5. Federal Research Center «All-Russian Research Institute of Experimental Veterinary Medicine n.a. K.I. Skryabin and Y.R. Kovalenko» of the Russian Academy of Sciences, Moscow, 109428 Russia;1. Department of Oncology and Plastic Surgery, Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of the Russian Federation, Moscow 119146, Russian Federation;2. Prokhorov General Physics Institute of the Russian Academy of Sciences, Vavilova st., 38, Moscow 119991, Russian Federation;3. National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Kashirskoe sh., 31, Moscow 115409, Russian Federation;4. Department of Oncology and Plastic Surgery, Academy of Postgraduate Education FSBI FNCC FMBA of Russia, Volokolamskoe sh., 91, Moscow 125371, Russian Federation;1. Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia;2. National Research Nuclear University “MEPhI”, 115409 Moscow, Russia;3. University Clinical Hospital No. 1, Levshin Institute of Cluster Oncology, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, 119435 Moscow, Russia
Abstract:BackgroundThe efficient intraoperative identification of tumors requires the development of highly specific near-infrared (NIR) probes as contrast agents. One of the most effective dyes existing in clinic oncology is Indocyanine Green (ICG). However, ICG has a rapid excretion, thus ruling out its extended accumulation in pathological tissues therefore limiting its clinical applications. ICG colloid solution (ICG NPs) consists predominantly of J-aggregates and to a lesser extent of H-aggregates and monomers. In the present study we assessed the spectral properties of ICG nanoforms in preclinical models.MethodsWe used optical spectroscopy and video fluorescence navigation to monitor accumulation and distribution of ICG monomers and ICG NPs in various tissues in mice with xenografted laryngopharyngeal carcinoma after intravenous drugs injection.ResultsAfter i.v. injection, the molecular form of ICG was not retained in the tumor and its circulation cycle averaged 5 min. Alternatively, the nanoform of the drug had a different pharmacokinetics, reaching maximum accumulation 24 h after intravenous injection. Moreover, once in the circulation, we observed a progressive accumulation in the tumor of both ICG H-aggregates and ICG monomers, but not J-aggregates.ConclusionSpectral characteristics of ICG NPs indicated the presence of several fractions, namely, J- and H-aggregates along with molecular forms. These fractions had different fluorescence spectra, allowing us to track the transformation of the drug in vivo conditions. After ICG NPs administration, J-aggregates induce accumulation of monomeric forms in the tumor, enabling extended intraoperative diagnostic, and as such further studies of J-aggregates for theranostic applications in oncological surgery are of great interest.
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