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

Authors

  • Suna Erdogan PhD,

    1. Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts
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    • The first two authors contributed equally to this work

  • Zdravka O. Medarova PhD,

    1. Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, MGH/Harvard Medical School, Boston, Massachusetts
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    • The first two authors contributed equally to this work

  • Aruna Roby PhD,

    1. Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts
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  • Anna Moore PhD,

    1. Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, MGH/Harvard Medical School, Boston, Massachusetts
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  • Vladimir P. Torchilin PhD, DSc

    Corresponding author
    1. Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts
    • Northeastern University, School of Pharmacy, Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, 312 Mugar Life Sciences Building, 360 Huntington Ave., Boston, MA, 02115
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Abstract

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 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.

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. J. Magn. Reson. Imaging 2008. © 2008 Wiley-Liss, Inc.

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