title: New dual mode gadolinium nanoparticle contrast agent for magnetic resonance imaging.
abstract: BACKGROUND
  Liposomal-based gadolinium (Gd) nanoparticles have elicited significant interest for use as blood pool and molecular magnetic resonance imaging (MRI) contrast agents. Previous generations of liposomal MR agents contained gadolinium-chelates either within the interior of liposomes (core-encapsulated gadolinium liposomes) or presented on the surface of liposomes (surface-conjugated gadolinium liposomes). We hypothesized that a liposomal agent that contained both core-encapsulated gadolinium and surface-conjugated gadolinium, defined herein as dual-mode gadolinium (Dual-Gd) liposomes, would result in a significant improvement in nanoparticle-based T1 relaxivity over the previous generations of liposomal agents. In this study, we have developed and tested, both in vitro and in vivo, such a dual-mode liposomal-based gadolinium contrast agent.
  
  
  RESULTS
  THREE TYPES OF LIPOSOMAL AGENTS WERE FABRICATED: core-encapsulated, surface-conjugated and dual-mode gadolinium liposomes. In vitro physico-chemical characterizations of the agents were performed to determine particle size and elemental composition. Gadolinium-based and nanoparticle-based T1 relaxivities of various agents were determined in bovine plasma. Subsequently, the agents were tested in vivo for contrast-enhanced magnetic resonance angiography (CE-MRA) studies. Characterization of the agents demonstrated the highest gadolinium atoms per nanoparticle for Dual-Gd liposomes. In vitro, surface-conjugated gadolinium liposomes demonstrated the highest T1 relaxivity on a gadolinium-basis. However, Dual-Gd liposomes demonstrated the highest T1 relaxivity on a nanoparticle-basis. In vivo, Dual-Gd liposomes resulted in the highest signal-to-noise ratio (SNR) and contrast-to-noise ratio in CE-MRA studies.
  
  
  CONCLUSIONS
  The dual-mode gadolinium liposomal contrast agent demonstrated higher particle-based T1 relaxivity, both in vitro and in vivo, compared to either the core-encapsulated or the surface-conjugated liposomal agent. The dual-mode gadolinium liposomes could enable reduced particle dose for use in CE-MRA and increased contrast sensitivity for use in molecular imaging.
authors.affiliation: School of Health Information Sciences, The University of Texas Health Sciences Center at Houston, Houston, Texas, USA.
authors.forename: Ketan B
authors.initials: KB
authors.lastname: Ghaghada
authors.forename: Murali
authors.initials: M
authors.lastname: Ravoori
authors.forename: Divya
authors.initials: D
authors.lastname: Sabapathy
authors.forename: James
authors.initials: J
authors.lastname: Bankson
authors.forename: Vikas
authors.initials: V
authors.lastname: Kundra
authors.forename: Ananth
authors.initials: A
authors.lastname: Annapragada
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000494:pharmacology*; D004337:Drug Carriers; D005682:Gadolinium / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000295:instrumentation* / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods; D010316:Particle Size; D013499:Surface Properties
chemical_list: D003287:Contrast Media; D004337:Drug Carriers; D008081:Liposomes; D005682:Gadolinium