Enhanced tumor MR imaging with gadolinium-loaded polychelating polymer-containing tumor-targeted liposomes

Purpose: 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. Materials and 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 Cd-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 RI 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 RI values at all investigated timepoints were significantly smaller. Conclusion: 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.