title: Development and Characterization of Novel LipoCEST Agents Based on Thermosensitive Liposomes.
abstract: OBJECTIVE
  To develop a novel probe for chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) based on thermosensitive liposomes (lipoCEST) for theranostics, in which diagnostics and therapy are integrated into a single platform.
  
  
  METHODS
  We developed two kinds of lipoCEST agents. The first kind encapsulated dysprosium (Dy)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-Na·3NaCl, terbium-DOTA-Na·3NaCl, or thulium-DOTA-Na·3NaCl into the inner cavity of thermosensitive liposomes, while the second kind encapsulated Dy-DOTA-Na and incorporated amphiphilic metal complex [thulium-diethylenetriamine pentaacetic acid-bis (stearylamide) (Tm-DTPA-BSA)] as a membrane constituent. The nuclear magnetic resonance (NMR)- and Z-spectra of these lipoCEST agents were acquired at various temperatures on a 9.4T MRI scanner. To investigate their applicability to the drug release induced by hyperthermia, we also encapsulated a fluorescent dye (calcein) into the inner cavity of liposomes and measured calcein release after warming them.
  
  
  RESULTS
  The intra- and extraliposomal water signals could be differentiated in all agents from their NMR- and Z-spectra. The agent incorporating Tm-DTPA-BSA showed the largest chemical shift (approximately 15 ppm) derived from the intraliposomal water protons. The calcein retained in this agent was successfully released at 44°C. The agent incorporating 30 mol% of Tm-DTPA-BSA in its membrane released more calcein at 42-44ºC than that of the agent incorporating 10 mol%.
  
  
  CONCLUSIONS
  We developed novel thermosensitive lipoCEST agents and characterized them. Our preliminary results suggest that they are useful and can be applied to theranostics.
authors: Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University.
authors: Shuki
authors: S
authors: Maruyama
authors: Junpei
authors: J
authors: Ueda
authors: Atsuomi
authors: A
authors: Kimura
authors: Kenya
authors: K
authors: Murase
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D008081:Liposomes; D013501:Surface-Active Agents