Enhanced tumor MR imaging with gadolinium-loaded polychelating polymer-containing tumor-targeted liposomes.
OBJECTIVE
To significantly enhance tumor MR imaging by using a contrast agent combining three components -- a long-circulating liposome, liposomal membrane-incorporated polychelating amphiphilic polymer heavily loaded with gadolinium, and cancer-specific monoclonal antibody 2C5 attached to the liposome surface.


METHODS
Tumor-bearing animals were imaged prior and 4, 24, and 48 hours after i.v. injection of 2C5-modified and unmodified Gd-PAP-containing PEGylated liposomes. The faster and more specific accumulation of the novel contrast nanoparticles in tumors was also confirmed by 3D angiograms and by direct visualization of Gd-immunoliposomes in tumor sections by confocal microscopy.


RESULTS
2C5-modified Gd-PAP-containing PEGylated liposomes allowed for fast and specific tumor imaging as early as 4 hours postinjection. T1 inversion recovery maps demonstrated a significant increase in tumor-associated R1 in animals injected with antibody-modified Gd-loaded liposomes 4 hours postinjection, followed by a gradual decrease consistent with clearance of the agent from the tumor region. In control animals injected with antibody-free liposomes the corresponding R1 values at all investigated timepoints were significantly smaller.


CONCLUSIONS
The results support the feasibility of using such multifunctional nanoparticular liposome-based agents simultaneously providing prolonged circulation, heavy Gd load, and specific cancer cell recognition as a superior contrast for MR tumor imaging.
Erdogan
Suna
S
Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.
Medarova
Zdravka O
ZO
Roby
Aruna
A
Moore
Anna
A
Torchilin
Vladimir P
VP
D000818:Animals; D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D005260:Female; D005682:Gadolinium; D008081:Liposomes; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000276:immunology; D011108:Polymers
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D008081:Liposomes; D011108:Polymers; D005682:Gadolinium