title: Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer.
abstract: Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).
authors.affiliation: Institute of Pharmaceutical Technology, Biocenter Niederursel, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany; Wilhelimnenspital, Institute of Nuclear Medicine, Montleartstr. 37, 1160 Wien, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Rosenberger
authors.affiliation: Department of Diagnostic Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Strauss
authors.affiliation: Department of General and Visceral Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dobiasch
authors.affiliation: Department of Diagnostic Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Weis
authors.affiliation: Department of General and Visceral Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Szanyi
authors.affiliation: CIC biomaGUNE, Molecular Imaging Unit, Paseo Miramón No 182, Parque Tecnológico de San Sebastián, 20009 San Sebastián, Guipúzcoa, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Gil-Iceta
authors.affiliation: CIC biomaGUNE, Molecular Imaging Unit, Paseo Miramón No 182, Parque Tecnológico de San Sebastián, 20009 San Sebastián, Guipúzcoa, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Alonso
authors.affiliation: CIC biomaGUNE, Molecular Imaging Unit, Paseo Miramón No 182, Parque Tecnológico de San Sebastián, 20009 San Sebastián, Guipúzcoa, Spain.
authors.forename: M
authors.initials: M
authors.lastname: González Esparza
authors.affiliation: CIC biomaGUNE, Molecular Imaging Unit, Paseo Miramón No 182, Parque Tecnológico de San Sebastián, 20009 San Sebastián, Guipúzcoa, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Gómez-Vallejo
authors.affiliation: CIC biomaGUNE, Molecular Imaging Unit, Paseo Miramón No 182, Parque Tecnológico de San Sebastián, 20009 San Sebastián, Guipúzcoa, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Szczupak
authors.affiliation: CIC biomaGUNE, Molecular Imaging Unit, Paseo Miramón No 182, Parque Tecnológico de San Sebastián, 20009 San Sebastián, Guipúzcoa, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Plaza-García
authors.affiliation: Wilhelimnenspital, Institute of Nuclear Medicine, Montleartstr. 37, 1160 Wien, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Mirzaei
authors.affiliation: Department of Chemistry & Institute of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: L L
authors.initials: LL
authors.lastname: Israel
authors.affiliation: Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bianchessi
authors.affiliation: Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Scanziani
authors.affiliation: Department of Chemistry & Institute of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: J-P
authors.initials: JP
authors.lastname: Lellouche
authors.affiliation: Wilhelimnenspital, Institute of Nuclear Medicine, Montleartstr. 37, 1160 Wien, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Knoll
authors.affiliation: Department of General and Visceral Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany; Department of General-, Visceral-, Transplantation-, Vascular- and Thorax-Surgery LMU Munich, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Werner
authors.affiliation: Department of General and Visceral Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Felix
authors.affiliation: Department of Diagnostic Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Grenacher
authors.affiliation: CIC biomaGUNE, Molecular Imaging Unit, Paseo Miramón No 182, Parque Tecnológico de San Sebastián, 20009 San Sebastián, Guipúzcoa, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Reese
authors.affiliation: Institute of Pharmaceutical Technology, Biocenter Niederursel, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt/Main, Germany. Electronic address: kreuter@em.uni-frankfurt.de.
authors.forename: J
authors.initials: J
authors.lastname: Kreuter
authors.affiliation: CIC biomaGUNE, Molecular Imaging Unit, Paseo Miramón No 182, Parque Tecnológico de San Sebastián, 20009 San Sebastián, Guipúzcoa, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Jiménez-González
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry; D037483:Galectin 1 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D058185:Magnetite Nanoparticles; D051379:Mice; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D023041:Xenograft Model Antitumor Assays
chemical_list: D005290:Ferric Compounds; D037483:Galectin 1; C445499:LGALS1 protein, human; D058185:Magnetite Nanoparticles; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D012709:Serum Albumin; C000499:ferric oxide; D010959:Tissue Plasminogen Activator
keywords: Handheld gamma camera; Maghemite; Magnetic resonance imaging (MRI); Single photon emission computed tomography–computer tomography (SPECT–CT); rHSA nanoparticles; t-PA-ligands to galectins; t-PApeptide1(LAC)