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

Elena N. Gerasimova1, Dmitrii Antugan2, Yana V. Tarakanchikova2,3, Albert R. Muslimov2,3, Alexander S. Timin2,4, Mikhail V. Zyuzin1,2

Development of effect ctive strategies for radionucl clide incorporation into CaCO3

3

particl cles for in in viv ivo st studies

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

Introduction Particle synthesis In vitro studies

68Ga Encapsulation

In vivo studies Conclusion

CaCl2 Na2CO3

68Ga

Layer-by-layer Microparticles Submicroparticles

Development of effect ctive strategies for radionucl clide incorporation into CaCO3 particl cles for in in viv ivo st studies

Introduction Particle synthesis In vitro studies 68Ga Encapsulation In vivo studies Conclusion

Non-invasive High-sensitive Visualization of small

• rgans

High-penetration capacity

Positron Emission Tomography CaCO3 particles

Straightforward synthesis Biocompatible Non-toxic High loading capacity Variability of parameters

Elena N. Gerasimova1, Dmitrii Antugan2, Yana V. Tarakanchikova2,3, Albert R. Muslimov2,3, Alexander S. Timin2,4, Mikhail V. Zyuzin1,2

Development of effect ctive strategies for radionucl clide incorporation into CaCO3 particl cles for in in viv ivo st studies

Introduction Particle synthesis In vitro studies

68Ga Encapsulation

In vivo studies Conclusion

The main goal: to develop different radiolabeling approaches of micrometric and submicrometric core-shell CaCO3 particles for an effective in vivo PET imaging. Tasks:

Na2CO3 CaCl2 CaCO3 Layer coating Submicrometric size Micrometric size

• 1. Particles synthesis and characterization
• 2. Toxicity studies
• 3. Radiolabeling strategies
• 4. In vivo visualization

Adsorption Layer coating Coprecipitation PET

Elena N. Gerasimova1, Dmitrii Antugan2, Yana V. Tarakanchikova2,3, Albert R. Muslimov2,3, Alexander S. Timin2,4, Mikhail V. Zyuzin1,2

Particle synthesis

Development of effect ctive strategies for radionucl clide incorporation into CaCO3 particl cles for in in viv ivo st studies

Introduction Particle synthesis In vitro studies

68Ga Encapsulation

In vivo studies Conclusion

500 nm

SEM image SEM image

1𝜈m

TEM image TEM image

CaCO3 CaCl2 Na2CO3 Layer coating by TA and HSA TA – Tannic Acid HSA – Human Serum Albumin

Characterization of micrometric CaCO3 particles Characterization of submicrometric CaCO3 particles Elena N. Gerasimova1, Dmitrii Antugan2, Yana V. Tarakanchikova2,3, Albert R. Muslimov2,3, Alexander S. Timin2,4, Mikhail V. Zyuzin1,2

Cells viability after 24h incubation with particles Live/dead assay after 24 h incubation with particles

Development of effect ctive strategies for radionucl clide incorporation into CaCO3 particl cles for in in viv ivo st studies

Introduction Particle synthesis In vitro studies

68Ga Encapsulation

In vivo studies Conclusion 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

Elena N. Gerasimova1, Dmitrii Antugan2, Yana V. Tarakanchikova2,3, Albert R. Muslimov2,3, Alexander S. Timin2,4, Mikhail V. Zyuzin1,2

68Ga encapsulation strategies

Development of effect ctive strategies for radionucl clide incorporation into CaCO3 particl cles for in in viv ivo st studies

Introduction Particle synthesis In vitro studies

68Ga Encapsulation

In vivo studies Conclusion

DOTA – The chelator molecule Chelator is a molecule for bonding of molecules to metal ions is 68Ga TA – Tannic Acid HSA – Human Serum Albumin CaCO3

68Ga+DOTA 68Ga

DOTA HSA

68Ga+DOTA

CaCO3 particles coated with HSA and TA Elena N. Gerasimova1, Dmitrii Antugan2, Yana V. Tarakanchikova2,3, Albert R. Muslimov2,3, Alexander S. Timin2,4, Mikhail V. Zyuzin1,2

Adsorption

Development of effect ctive strategies for radionucl clide incorporation into CaCO3 particl cles for in in viv ivo st studies

Introduction Particle synthesis In vitro studies

68Ga Encapsulation

In vivo studies Conclusion

Layer coating Co-precipitation Elena N. Gerasimova1, Dmitrii Antugan2, Yana V. Tarakanchikova2,3, Albert R. Muslimov2,3, Alexander S. Timin2,4, Mikhail V. Zyuzin1,2

Development of effect ctive strategies for radionucl clide incorporation into CaCO3 particl cles for in in viv ivo st studies

Introduction Particle synthesis In vitro studies

68Ga Encapsulation

In vivo studies Conclusion

The efficiency of the encapsulation А. Bounding efficiency of 68Ga-DOTA-HSA and 68Ga-DOTA with particles

• C. In vitro stability in human serum.

Blood plasma

• B. Retention efficiency of 68Ga-DOTA-HSA and 68Ga-DOTA within particles

Washing with PBS 5 times

Elena N. Gerasimova1, Dmitrii Antugan2, Yana V. Tarakanchikova2,3, Albert R. Muslimov2,3, Alexander S. Timin2,4, Mikhail V. Zyuzin1,2

Development of effect ctive strategies for radionucl clide incorporation into CaCO3 particl cles for in in viv ivo st studies

Introduction Particle synthesis In vitro studies

68Ga Encapsulation

In vivo studies Conclusion

PET/CT images at different time points

90 min 180 min 10 min 90 min 180 min

68Ga-MicCSPs 68Ga-SubCSPs 68Ga-DOTA 68Ga-DOTA-HSA

10 min High Low

The biodistribution profile by radiometric analysis

68Ga-micrometric CaCO3 particles 68Ga-submicrometric CaCO3 particles 68Ga-DOTA 68Ga-DOTA -HSA

Elena N. Gerasimova1, Dmitrii Antugan2, Yana V. Tarakanchikova2,3, Albert R. Muslimov2,3, Alexander S. Timin2,4, Mikhail V. Zyuzin1,2

Development of effect ctive strategies for radionucl clide incorporation into CaCO3 particl cles for in in viv ivo st studies

Introduction Particle synthesis In vitro studies

68Ga Encapsulation

In vivo studies Conclusion

Results

1. Different radiolabeling strategies of CaCO3 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

• f retention efficiency and in vitro stability) strategy to load 68Ga.

3. In vivo experiments on rats reveled passive accumulation 68Ga-Micrometric particles in the lungs; 68Ga- 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 Elena N. Gerasimova1, Dmitrii Antugan2, Yana V. Tarakanchikova2,3, Albert R. Muslimov2,3, Alexander S. Timin2,4, Mikhail V. Zyuzin1,2