Lanthanide-loaded liposomes for multimodality imaging and therapy.
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.
Zielhuis
Sander W
SW
Department of Nuclear Medicine, University Medical Center, Utrecht, The Netherlands.
Seppenwoolde
Jan-Henry
JH
Mateus
Vanessa A P
VA
Bakker
Chris J G
CJ
Krijger
Gerard C
GC
Storm
Gert
G
Zonnenberg
Bernard A
BA
van het Schip
Alfred D
AD
Koning
Gerben A
GA
Nijsen
Johannes F W
JF
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*
D028581:Lanthanoid Series Elements; D008081:Liposomes; D013667:Technetium