Targeting of MPEG-protected polyamino acid carrier to human E-selectin in vitro |
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| Authors: | Kang H W Weissleder R Bogdanov A |
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| Institution: | (1) Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Maryland, U.S.A., US |
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| Abstract: | Summary. Targeted diagnostic agents are expected to have a significant impact in molecular imaging of cell-surface associated markers
of proliferation, inflammation and angiogenesis. In this communication, we describe a new class of targeted polyamino acid-based
protected graft copolymers (PGC) of poly-(L-lysine) and methyl poly-(ethylene glycol) (PGC) covalently conjugated with a monoclonal
antibody fragment, F(ab′)2. We utilized targeted PGC conjugates as carriers of near-infrared indocyanine fluorophores (Cy5.5) for optical imaging of
endothelial cell populations expressing IL-1β inducible proinflammatory marker E-selectin. We compared two conjugation chemistries, involving either introduction of sulfhydryl
group to F(ab′)2, or via direct attachment of the antibody fragment directly to the chemically activated PGC. Both PGC-based targeted agents
demonstrated high binding specificity (20–30 fold over non-specific uptake) and were utilized for imaging E-selectin expression
on human endothelial cells activated with IL-1β.
Received June 29, 2001 Accepted August 8, 2001 Published online August 9, 2002 |
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| Keywords: | : E-selectin Endothelium IL-1β Graft copolymer Indocyanine Antibody Optical imaging |
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