Irene Tsiapa1, Eleni K Efthimiadou2, Eirini Fragogeorgi3, George Loudos4, Alexandra D Varvarigou5, Penelope Bouziotis5, George C Kordas6, Dimitris Mihailidis7, George C Nikiforidis6, Stavros Xanthopoulos5, Dimitrios Psimadas3, Maria Paravatou-Petsotas5, Lazaros Palamaris4, John D Hazle8, George C Kagadis9. 1. Department of Medical Physics, School of Medicine, University of Patras, Patra, Greece; Institute for Nuclear and Radiological Sciences, Energy, Technology and Safety, National Center of Scientific Research "Demokritos", Aghia Paraskevi-Athens, Greece. 2. Sol-Gel Laboratory, Institute for Advanced Materials, Physicochemical Processes, Nanotechnology & Microsystems, NCSR "Demokritos", Aghia Paraskevi-Athens, Greece. 3. Department of Biomedical Technology Engineering, TEI of Athens, Aigaleo-Athens, Greece; Institute for Nuclear and Radiological Sciences, Energy, Technology and Safety, National Center of Scientific Research "Demokritos", Aghia Paraskevi-Athens, Greece. 4. Department of Biomedical Technology Engineering, TEI of Athens, Aigaleo-Athens, Greece. 5. Institute for Nuclear and Radiological Sciences, Energy, Technology and Safety, National Center of Scientific Research "Demokritos", Aghia Paraskevi-Athens, Greece. 6. Department of Medical Physics, School of Medicine, University of Patras, Patra, Greece. 7. Charleston Radiation Therapy Consultants, Charleston, WV 253 04, USA. 8. Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 9. Department of Medical Physics, School of Medicine, University of Patras, Patra, Greece; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: gkagad@gmail.com.
Abstract
HYPOTHESIS: Dual-modality imaging agents, such as radiolabeled iron oxide nanoparticles (IO-NPs), are promising candidates for cancer diagnosis and therapy. We developed and evaluated aminosilane coated Fe3O4 (10±2nm) as a tumor imaging agent in nuclear medicine through 3-aminopropyltriethoxysilane (APTES) functionalization. We evaluated this multimeric system of targeted (99m)Tc-labeled nanoparticles (NPs) conjugated with a new RGD derivate (cRGDfK-Orn3-CGG), characterized as NPs-RGD as a potential thermal therapy delivery vehicle. EXPERIMENTS: Transmission Electron Microscopy (TEM) and spectroscopy techniques were used to characterize the IO-NPs indicating their functionalization with peptides. Radiolabeled IO-NPs (targeted, non-targeted) were evaluated with regard to their radiochemical, radiobiological and imaging characteristics. In vivo studies were performed in normal and ανβ3-positive tumor (U87MG glioblastoma) bearing mice. We also demonstrated that this system could reach ablative temperatures in vivo. FINDINGS: Both radiolabeled IO-NPs were obtained in high radiochemical yield (>98%) and proved stable in vitro. The in vivo studies for both IO-NPs have shown significant liver and spleen uptake at all examined time points in normal and U87MG glioblastoma tumor-bearing mice, due to their colloidal nature. We have confirmed through in vivo biodistribution studies that the non-targeted (99m)Tc-NPs poorly internalized in the tumor, while the targeted (99m)Tc-NPs-RGD, present 9-fold higher tumor accumulation at 1h p.i. Accumulation of both IO-NPs in other organs was negligible. Blocking experiments indicated target specificity for integrin receptors in U87MG glioblastoma cells. The preliminary in vivo study of applied alternating magnetic field showed that the induced hyperthermia is feasible due to the aid of IO-NPs.
HYPOTHESIS: Dual-modality imaging agents, such as radiolabeled iron oxide nanoparticles (IO-NPs), are promising candidates for cancer diagnosis and therapy. We developed and evaluated aminosilane coated Fe3O4 (10±2nm) as a tumor imaging agent in nuclear medicine through 3-aminopropyltriethoxysilane (APTES) functionalization. We evaluated this multimeric system of targeted (99m)Tc-labeled nanoparticles (NPs) conjugated with a new RGD derivate (cRGDfK-Orn3-CGG), characterized as NPs-RGD as a potential thermal therapy delivery vehicle. EXPERIMENTS: Transmission Electron Microscopy (TEM) and spectroscopy techniques were used to characterize the IO-NPs indicating their functionalization with peptides. Radiolabeled IO-NPs (targeted, non-targeted) were evaluated with regard to their radiochemical, radiobiological and imaging characteristics. In vivo studies were performed in normal and ανβ3-positive tumor (U87MG glioblastoma) bearing mice. We also demonstrated that this system could reach ablative temperatures in vivo. FINDINGS: Both radiolabeled IO-NPs were obtained in high radiochemical yield (>98%) and proved stable in vitro. The in vivo studies for both IO-NPs have shown significant liver and spleen uptake at all examined time points in normal and U87MG glioblastoma tumor-bearing mice, due to their colloidal nature. We have confirmed through in vivo biodistribution studies that the non-targeted (99m)Tc-NPs poorly internalized in the tumor, while the targeted (99m)Tc-NPs-RGD, present 9-fold higher tumor accumulation at 1h p.i. Accumulation of both IO-NPs in other organs was negligible. Blocking experiments indicated target specificity for integrin receptors in U87MG glioblastoma cells. The preliminary in vivo study of applied alternating magnetic field showed that the induced hyperthermia is feasible due to the aid of IO-NPs.
Authors: Irene Tsiapa; George Loudos; Eirini A Fragogeorgi; Penelope Bouziotis; Dimitrios Psimadas; Stavros Xanthopoulos; Maria Paravatou-Petsotas; Lazaros Palamaris; Alexandra D Varvarigou; Dimitris Karnabatidis; George C Kagadis Journal: Cancer Biother Radiopharm Date: 2014-12 Impact factor: 3.099
Authors: Mohamed M Swidan; Omnya M Khowessah; Mohamed Abd El-Motaleb; Ahmed Abd El-Bary; Mohamed T El-Kolaly; Tamer M Sakr Journal: Daru Date: 2019-01-31 Impact factor: 3.117