title: Novel nano-sized MR contrast agent mediates strong tumor contrast enhancement in an oncogene-driven breast cancer model.
abstract: The current study was carried out to test the potential of a new nanomaterial (Spago Pix) as a macromolecular magnetic MR contrast agent for tumor detection and to verify the presence of nanomaterial in tumor tissue. Spago Pix, synthesized by Spago Nanomedical AB, is a nanomaterial with a globular shape, an average hydrodynamic diameter of 5 nm, and a relaxivity (r1) of approximately 30 (mM Mn)-1 s-1 (60 MHz). The material consists of an organophosphosilane hydrogel with strongly chelated manganese (II) ions and a covalently attached PEG surface layer. In vivo MRI of the MMTV-PyMT breast cancer model was performed on a 3 T clinical scanner. Tissues were thereafter analyzed for manganese and silicon content using inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The presence of nanomaterial in tumor and muscle tissue was assessed using an anti-PEG monoclonal antibody. MR imaging of tumor-bearing mice (n = 7) showed a contrast enhancement factor of 1.8 (tumor versus muscle) at 30 minutes post-administration. Contrast was retained and further increased 2-4 hours after administration. ICP-AES and immunohistochemistry confirmed selective accumulation of nanomaterial in tumor tissue. A blood pharmacokinetics analysis showed that the concentration of Spago Pix gradually decreased over the first hour, which was in good agreement with the time frame in which the accumulation in tumor occurred. In summary, we demonstrate that Spago Pix selectively enhances MR tumor contrast in a clinically relevant animal model. Based on the generally higher vascular leakiness in malignant compared to benign tissue lesions, Spago Pix has the potential to significantly improve cancer diagnosis and characterization by MRI.
authors.affiliation: Spago Nanomedical, Lund, Sweden.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Eriksson
authors.affiliation: Spago Nanomedical, Lund, Sweden.
authors.forename: Emil
authors.initials: E
authors.lastname: Aaltonen
authors.affiliation: Spago Nanomedical, Lund, Sweden.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Petoral
authors.affiliation: Spago Nanomedical, Lund, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Lauritzson
authors.affiliation: Department of Laboratory Medicine Lund, Division of Translational Cancer Research, Lund University, Lund, Sweden.
authors.forename: Hideki
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Department of Laboratory Medicine Lund, Division of Translational Cancer Research, Lund University, Lund, Sweden; Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kristian
authors.initials: K
authors.lastname: Pietras
authors.affiliation: Department of Medical Radiation Physics, Lund University, Skåne University Hospital, Malmö, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Månsson
authors.affiliation: Spago Nanomedical, Lund, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hansson
authors.affiliation: Department of Radiology, Lund University, Skåne University Hospital, Malmö, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Leander
authors.affiliation: Spago Nanomedical, Lund, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Axelsson
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis*; D003287:Contrast Media / Q000737:chemistry*; D004195:Disease Models, Animal; D005260:Female; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009943:Organophosphorus Compounds / Q000737:chemistry
chemical_list: D003287:Contrast Media; D009943:Organophosphorus Compounds; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate