title: Noninvasive Imaging of Liposomal Delivery of Superparamagnetic Iron Oxide Nanoparticles to Orthotopic Human Breast Tumor in Mice.
abstract: OBJECTIVE
  Magnetic resonance imaging (MRI) is widely used for diagnostic imaging in preclinical studies and in clinical settings. Considering the intrinsic low sensitivity and poor specificity of standard MRI contrast agents, the enhanced delivery of MRI tracers into tumors is an important challenge to be addressed. This study was intended to investigate whether delivery of superparamagnetic iron oxide nanoparticles (SPIONs) can be enhanced by liposomal SPION formulations for either "passive" delivery into tumor via the enhanced permeability and retention (EPR) effect or "active" targeted delivery to tumor endothelium via the receptors for vascular endothelial growth factor (VEGFRs).
  
  
  METHODS
  In vivo MRI of orthotopic MDA-MB-231 tumors was performed on a preclinical 9.4 T MRI scanner following intravenous administration of either free/non-targeted or targeted liposomal SPIONs.
  
  
  RESULTS
  In vivo MRI study revealed that only the non-targeted liposomal formulation provided a statistically significant accumulation of SPIONs in the tumor at four hours post-injection. The EPR effect contributes to improved accumulation of liposomal SPIONs in tumors compared to the presumably more transient retention during the targeting of the tumor vasculature via VEGFRs.
  
  
  CONCLUSIONS
  A non-targeted liposomal formulation of SPIONs could be the optimal option for MRI detection of breast tumors and for the development of therapeutic liposomes for MRI-guided therapy.
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.|Life Science Tokyo Advanced Research Center (L-StaR), Hoshi University School of Pharmacy and Pharmaceutical Science, Shinagawa-ku, Tokyo, JAPAN (Current affiliation).
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Wenlian
authors.initials: W
authors.lastname: Zhu
authors.affiliation: SibTech, Inc., Brookfield, CT 06804, USA.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Backer
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Neoh
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Sudath
authors.initials: S
authors.lastname: Hapuarachchige
authors.affiliation: CadenzaMed LLC, Wayne, PA 19087, USA.
authors.forename: Susanta K
authors.initials: SK
authors.lastname: Sarkar
authors.affiliation: SibTech, Inc., Brookfield, CT 06804, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Backer
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Artemov
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D013499:Surface Properties; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D008081:Liposomes; D058185:Magnetite Nanoparticles; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D040262:Receptors, Vascular Endothelial Growth Factor; D052203:Ferrosoferric Oxide
keywords: liposomes; magnetic resonance imaging (MRI); passive targeting; single-chain vascular endothelial growth factor (scVEGF); superparamagnetic iron oxide nanoparticles (SPIONs)