title: Lanthanide-loaded liposomes for multimodality imaging and therapy.
abstract: Many advanced molecular imaging agents are currently being investigated preclinically. Especially, liposomes, have proven to be very promising carrier systems for diagnostic agents for use in single-photon emission computed tomography (SPECT) or magnetic resonance imaging (MRI), as well as for therapeutic agents to treat diseases such as cancer. In this study, nanosized liposomes were designed and labeled with the radionuclides, holmium-166 (both a beta- and gamma-emitter and also highly paramagnetic) or technetium-99m, and coloaded with paramagnetic gadolinium allowing multimodality SPECT and MR imaging and radionuclide therapy with one single agent.
  
  
  METHODS
  Diethylenetriaminepentaacetic acid bisoctadecylamide (an amphiphilic molecule with a chelating group suitable for labeling with radionuclides) and gadoliniumacetylacetonate (GdAcAc) (a small lipophilic paramagnetic molecule) were incorporated in liposomes. The liposomes were characterized by measuring their mean size and size distribution, gadolinium content, and radiochemical stability after incubation in human serum at 37 degrees C. The MRI properties (in vitro) were determined by use of relaxivity measurements at 1.5 and 3.0 Tesla in order to evaluate their potency as imaging agents.
  
  
  RESULTS
  The liposomes were successfully labeled with holmium-166, resulting in a high labeling efficiency (95% +/- 1%) and radiochemical stability (> 98% after 48 hours of incubation), and coloaded with GdAcAc. Labeling of liposomes with technetium-99m was somewhat less efficient (85% +/- 2%), although their radiochemical stability was sufficient (95% +/- 1% after 6 hours of incubation). MRI measurements showed that the incorporation of GdAcAc had a strong effect on the MRI relaxivity.
  
  
  CONCLUSIONS
  The synthesized liposomes allow for multimodality imaging and therapy, which makes these new agents highly attractive for future applications.
authors.affiliation: Department of Nuclear Medicine, University Medical Center, Utrecht, The Netherlands.
authors.forename: Sander W
authors.initials: SW
authors.lastname: Zielhuis
authors.forename: Jan-Henry
authors.initials: JH
authors.lastname: Seppenwoolde
authors.forename: Vanessa A P
authors.initials: VA
authors.lastname: Mateus
authors.forename: Chris J G
authors.initials: CJ
authors.lastname: Bakker
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Krijger
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Zonnenberg
authors.forename: Alfred D
authors.initials: AD
authors.lastname: van het Schip
authors.forename: Gerben A
authors.initials: GA
authors.lastname: Koning
authors.forename: Johannes F W
authors.initials: JF
authors.lastname: Nijsen
mesh_terms: D028581:Lanthanoid Series Elements / Q000008:administration & dosage*; D008081:Liposomes / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage; D013667:Technetium / Q000008:administration & dosage; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D028581:Lanthanoid Series Elements; D008081:Liposomes; D013667:Technetium