Structural Effects on the Biodistribution and Positron Emission Tomography (PET) Imaging of Well-Defined 64Cu-Labeled Nanoparticles Comprised of Amphiphilic Block Graft Copolymers

Eric D. Pressly,† Raffaella Rossin,‡ Aviv Hagooly,‡ Ken-ichi Fukukawa,† Benjamin W. Messmore,† Michael J. Welch,*‡§ Karen L. Wooley,*‡§ Matthew S. Lamm, Rohan A. Hule, Darrin J. Pochan, and Craig J. Hawker*†
Materials Research Laboratory, Departments of Chemistry, Biochemistry and Materials, University of California, Santa Barbara, California 93106, Divisions of Chemistry and Radiological Sciences, Washington University, St. Louis, Missouri 63110, and Materials Science and Engineering, University of Delaware, Newark, Delaware 19716
Biomacromolecules, 2007, 8 (10), pp 3126–3134
DOI: 10.1021/bm700541e
Publication Date (Web): September 20, 2007
Copyright © 2007 American Chemical Society
†

 University of California, Santa Barbara.

,

 These authors contributed equally to this work.

,
‡

 Division of Radiological Sciences, Washington University School of Medicine.

,
*

 To whom correspondence should be addressed. Telephone:  (805) 893-7161. Fax:  (805) 893-8797. E-mail:  hawker@mrl.ucsb.edu.

,
§

 Division of Chemistry, Washington University.

,

 University of Delaware.

Abstract

Abstract Image

The synthesis of poly(methyl methacrylate-co-methacryloxysuccinimide-graft-poly(ethylene glycol)) (PMMA-co-PMASI-g-PEG) via living free radical polymerization provides a convenient route to well-defined amphiphilic graft copolymers having a controllable number of reactive functional groups, variable length PEG grafts, and low polydispersity. These copolymers were shown to form PMMA-core/PEG-shell nanoparticles upon hydrophobic collapse in water, with the hydrodynamic size being defined by the molecular weight of the backbone and the PEG grafts. Functionalization of these polymeric nanoparticles with a 1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) ligand capable of chelating radioactive 64Cu nuclei enabled the biodistribution and in vivo positron emission tomography of these materials to be studied and directly correlated to the initial structure. Results indicate that nanoparticles with increasing PEG chain lengths show increased blood circulation and low accumulation in excretory organs, suggesting the possible use of these materials as stealth carriers for medical imaging and systemic administration.

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History

  • Published In Issue October 08, 2007
  • Received May 16, 2007
    Revised Manuscript Received July 30, 2007

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