Development of effect ctive strategies for radionucl clide - PowerPoint PPT Presentation

Development of effect ctive strategies for radionucl clide incorporation into CaCO 3 3 particl cles for in in viv ivo st studies Elena N. Gerasimova 1 , Dmitrii Antugan 2 , Yana V. Tarakanchikova 2,3 , Albert R. Muslimov 2,3 , Alexander S. Timin 2,4 , Mikhail V. Zyuzin 1,2 1.Department of Physics and Engineering, ITMO University, Lomonosova 9, 191002, St. Petersburg, Russian Federation 2.Russian Research Center of Radiology and Surgical Technologies named after A. M. Granov (RRCRST) of Ministry of Public Health 3.Nanobiotechnology Laboratory, St. Petersburg Academic University 4.Research School of Chemical and Biomedical Engineering, National Research Tomsk Polytechnic University Particle synthesis In vitro studies 68 Ga Encapsulation Introduction In vivo studies Conclusion 68 Ga Microparticles CaCl 2 Na 2 CO 3 Layer-by-layer Submicroparticles

Development of effect ctive strategies for radionucl clide incorporation into CaCO 3 particl cles for in in viv ivo st studies Elena N. Gerasimova 1 , Dmitrii Antugan 2 , Yana V. Tarakanchikova 2,3 , Albert R. Muslimov 2,3 , Alexander S. Timin 2,4 , Mikhail V. Zyuzin 1,2 Conclusion Introduction Particle synthesis In vitro studies 68Ga Encapsulation In vivo studies Visualization of small Non-invasive Straightforward Variability of organs synthesis parameters CaCO 3 particles Positron Emission Non-toxic High loading Tomography capacity High-penetration High-sensitive capacity Biocompatible

Development of effect ctive strategies for radionucl clide incorporation into CaCO 3 particl cles for in in viv ivo st studies Elena N. Gerasimova 1 , Dmitrii Antugan 2 , Yana V. Tarakanchikova 2,3 , Albert R. Muslimov 2,3 , Alexander S. Timin 2,4 , Mikhail V. Zyuzin 1,2 Introduction Particle synthesis In vitro studies 68 Ga Encapsulation In vivo studies Conclusion The main goal: to develop different radiolabeling approaches of micrometric and submicrometric core-shell CaCO 3 particles for an effective in vivo PET imaging. Tasks: Submicrometric Na 2 CO 3 CaCl 2 CaCO 3 size 1. Particles synthesis and characterization Layer coating Micrometric size 2. Toxicity studies 3. Radiolabeling strategies Layer Adsorption Coprecipitation coating 4. In vivo visualization PET

Development of effect ctive strategies for radionucl clide incorporation into CaCO 3 particl cles for in in viv ivo st studies Elena N. Gerasimova 1 , Dmitrii Antugan 2 , Yana V. Tarakanchikova 2,3 , Albert R. Muslimov 2,3 , Alexander S. Timin 2,4 , Mikhail V. Zyuzin 1,2 Introduction Particle synthesis In vitro studies 68 Ga Encapsulation In vivo studies Conclusion Characterization of micrometric CaCO 3 particles Particle synthesis Na 2 CO 3 SEM image TEM image CaCl 2 CaCO 3 1 𝜈 m Characterization of submicrometric CaCO 3 particles Layer coating by TA and SEM image TEM image HSA TA – Tannic Acid HSA – Human Serum Albumin 500 nm

Development of effect ctive strategies for radionucl clide incorporation into CaCO 3 particl cles for in in viv ivo st studies Elena N. Gerasimova 1 , Dmitrii Antugan 2 , Yana V. Tarakanchikova 2,3 , Albert R. Muslimov 2,3 , Alexander S. Timin 2,4 , Mikhail V. Zyuzin 1,2 Introduction Particle synthesis In vitro studies 68 Ga Encapsulation In vivo studies Conclusion Live/dead assay after 24 h incubation with particles Cells viability after 24h incubation with particles TA – MicCSPs - Microparticles HS – SubCSPs –Submicroparticles Living cells were stained with Calcein AM (green) Dead cells were stained with propidium iodide (red). HeLa cells – model of cancerous cells hMSCs - Human mesenchymal steam cells

Development of effect ctive strategies for radionucl clide incorporation into CaCO3 particl cles for in in viv ivo st studies Elena N. Gerasimova 1 , Dmitrii Antugan 2 , Yana V. Tarakanchikova 2,3 , Albert R. Muslimov 2,3 , Alexander S. Timin 2,4 , Mikhail V. Zyuzin 1,2 Introduction Particle synthesis In vitro studies 68 Ga Encapsulation In vivo studies Conclusion 68 Ga encapsulation strategies DOTA – The chelator molecule Chelator is a molecule for bonding of molecules to metal ions is 68 Ga 68 Ga TA – Tannic Acid HSA – Human Serum Albumin DOTA 68 Ga+DOTA CaCO 3 CaCO 3 particles coated 68 Ga+DOTA HSA with HSA and TA

Development of effect ctive strategies for radionucl clide incorporation into CaCO 3 particl cles for in in viv ivo st studies Elena N. Gerasimova 1 , Dmitrii Antugan 2 , Yana V. Tarakanchikova 2,3 , Albert R. Muslimov 2,3 , Alexander S. Timin 2,4 , Mikhail V. Zyuzin 1,2 Introduction Particle synthesis In vitro studies 68 Ga Encapsulation In vivo studies Conclusion Co-precipitation Adsorption Layer coating

Development of effect ctive strategies for radionucl clide incorporation into CaCO 3 particl cles for in in viv ivo st studies Elena N. Gerasimova 1 , Dmitrii Antugan 2 , Yana V. Tarakanchikova 2,3 , Albert R. Muslimov 2,3 , Alexander S. Timin 2,4 , Mikhail V. Zyuzin 1,2 Introduction Particle synthesis In vitro studies 68 Ga Encapsulation In vivo studies Conclusion The efficiency of the encapsulation А. Bounding efficiency of 68 Ga-DOTA-HSA and 68 Ga-DOTA with particles B. Retention efficiency of 68 Ga-DOTA-HSA and 68 Ga-DOTA within particles Washing with PBS 5 times C. In vitro stability in human serum. Blood plasma

Development of effect ctive strategies for radionucl clide incorporation into CaCO 3 particl cles for in in viv ivo st studies Elena N. Gerasimova 1 , Dmitrii Antugan 2 , Yana V. Tarakanchikova 2,3 , Albert R. Muslimov 2,3 , Alexander S. Timin 2,4 , Mikhail V. Zyuzin 1,2 Introduction Particle synthesis In vitro studies 68 Ga Encapsulation In vivo studies Conclusion The biodistribution profile by radiometric analysis PET/CT images at different time points Low High 68 Ga-MicCSPs 68 Ga-DOTA 68 Ga-SubCSPs 68 Ga-DOTA-HSA 68 Ga-micrometric CaCO 3 particles 68 Ga-submicrometric CaCO 3 particles 68 Ga-DOTA 10 min 90 min 180 min 180 min 10 min 90 min 68 Ga-DOTA -HSA

Development of effect ctive strategies for radionucl clide incorporation into CaCO 3 particl cles for in in viv ivo st studies Elena N. Gerasimova 1 , Dmitrii Antugan 2 , Yana V. Tarakanchikova 2,3 , Albert R. Muslimov 2,3 , Alexander S. Timin 2,4 , Mikhail V. Zyuzin 1,2 Introduction Particle synthesis In vitro studies 68 Ga Encapsulation In vivo studies Conclusion Results 1. Different radiolabeling strategies of CaCO 3 particles were developed: adsorption, layer coating and co- precipitation. 2. Among the tested encapsulation methods, coprecipitation loading strategy is the most efficient (in the order of retention efficiency and in vitro stability) strategy to load 68 Ga. 3. In vivo experiments on rats reveled passive accumulation 68 Ga-Micrometric particles in the lungs; 68 Ga- Submicrometric particles were accumulated in the liver and spleen. Conferences and publications 1. M. V. Zyuzin, E. N. Gerasimova et al. Radiolabeling strategies of micron- and submicron sized core-shell carriers for in vivo studies. ACS Appl. Mater. Interfaces, 2020, DOI:10.1021/acsami.0c06996 2. Elena N. Gerasimova, “Delivery of radionuclides using biocompatible calcium carbonate particles.”, ITMO Open Science 2020, poster Contact: elena.gerasimova@metalab.ifmo.ru