title: (99m)Tc-labeled aminosilane-coated iron oxide nanoparticles for molecular imaging of ανβ3-mediated tumor expression and feasibility for hyperthermia treatment.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.affiliation: 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.
authors.forename: Irene
authors.initials: I
authors.lastname: Tsiapa
authors.affiliation: Sol-Gel Laboratory, Institute for Advanced Materials, Physicochemical Processes, Nanotechnology & Microsystems, NCSR "Demokritos", Aghia Paraskevi-Athens, Greece.
authors.forename: Eleni K
authors.initials: EK
authors.lastname: Efthimiadou
authors.affiliation: 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.
authors.forename: Eirini
authors.initials: E
authors.lastname: Fragogeorgi
authors.affiliation: Department of Biomedical Technology Engineering, TEI of Athens, Aigaleo-Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Loudos
authors.affiliation: Institute for Nuclear and Radiological Sciences, Energy, Technology and Safety, National Center of Scientific Research "Demokritos", Aghia Paraskevi-Athens, Greece.
authors.forename: Alexandra D
authors.initials: AD
authors.lastname: Varvarigou
authors.affiliation: Institute for Nuclear and Radiological Sciences, Energy, Technology and Safety, National Center of Scientific Research "Demokritos", Aghia Paraskevi-Athens, Greece.
authors.forename: Penelope
authors.initials: P
authors.lastname: Bouziotis
authors.affiliation: Department of Medical Physics, School of Medicine, University of Patras, Patra, Greece.
authors.forename: George C
authors.initials: GC
authors.lastname: Kordas
authors.affiliation: Charleston Radiation Therapy Consultants, Charleston, WV 253 04, USA.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mihailidis
authors.affiliation: Department of Medical Physics, School of Medicine, University of Patras, Patra, Greece.
authors.forename: George C
authors.initials: GC
authors.lastname: Nikiforidis
authors.affiliation: Institute for Nuclear and Radiological Sciences, Energy, Technology and Safety, National Center of Scientific Research "Demokritos", Aghia Paraskevi-Athens, Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Xanthopoulos
authors.affiliation: 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.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Psimadas
authors.affiliation: Institute for Nuclear and Radiological Sciences, Energy, Technology and Safety, National Center of Scientific Research "Demokritos", Aghia Paraskevi-Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Paravatou-Petsotas
authors.affiliation: Department of Biomedical Technology Engineering, TEI of Athens, Aigaleo-Athens, Greece.
authors.forename: Lazaros
authors.initials: L
authors.lastname: Palamaris
authors.affiliation: Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Hazle
authors.affiliation: 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.
authors.forename: George C
authors.initials: GC
authors.lastname: Kagadis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D006979:Hyperthermia, Induced; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis*; D007553:Isotope Labeling; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D011437:Propylamines; D012821:Silanes / Q000737:chemistry; D013667:Technetium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D005290:Ferric Compounds; D039302:Integrin alphaVbeta3; D009363:Neoplasm Proteins; D011437:Propylamines; D012821:Silanes; C000499:ferric oxide; D013667:Technetium; C477625:amino-propyl-triethoxysilane
keywords: Hyperthermia; Integrin; Nanoparticles; RGD; Radiolabeling; Technetium