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

Pressly ED, Rossin R, Hagooly A, Fukukawa KI, Messmore BW, Welch MJ, Wooley KL, Lamm MS, Hule RA, Pochan DJ, Hawker CJ

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.

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.

Published 20 September 2007 in Biomacromolecules.
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