Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging.

TitleSize optimization of synthetic graft copolymers for in vivo angiogenesis imaging.
Publication TypeJournal Article
Year of Publication2001
AuthorsWeissleder R, Bogdanov A, Tung CH, Weinmann HJ
JournalBioconjug Chem
Volume12
Issue2
Pagination213-9
Date Published2001 Mar-Apr
ISSN1043-1802
KeywordsAnimals, Contrast Media, Endothelial Growth Factors, Extravasation of Diagnostic and Therapeutic Materials, Female, Heterocyclic Compounds, 1-Ring, Humans, Lymphokines, Magnetic Resonance Imaging, Mammary Neoplasms, Experimental, Metals, Rare Earth, Mice, Mice, Nude, Microscopy, Fluorescence, Molecular Structure, Molecular Weight, Neoplasm Transplantation, Neovascularization, Pathologic, Particle Size, Polyethylene Glycols, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors
Abstract

Angiogenesis is a critical step in tumor development and more than 25 angiogenesis inhibitors are currently in clinical trials. Noninvasive in vivo imaging of angiogenesis represents a unique opportunity of repeatedly quantitating microvascular parameters prior to and during anti-angiogenic treatments. While several imaging tracers have been proposed for MR and nuclear imaging, there does not exist any consensus of what constitutes an ideal size of an imaging agent. A series of synthetic pegylated DOTA derivatized graft copolymers (30, 60, 120 kDa) were synthesized and their in vivo behavior tested in two breast cancer models differing in vascular endothelial growth factor (VEGF) expression. Polymers were labeled with different lanthanides (Eu, Gd, Dy) and absolute blood and tumor concentrations were determined by ICP-AES measurements. DOTA and the 30 kDa polymers underwent renal clearance resulting in low plasma levels. Slow leakage across neovasculature into tumor interstitium was clearly dependent on the molecular mass of all tested agents in MCF-7 tumors. However, a cutoff was observed with minimal extravasation occurring at and above 120 kDa in well differentiated MCF-7 tumors. VEGF overexpression caused detectable differences in extravasation of all polymers, including the 120 kDa compound. We conclude that large molecular weight contrast agents with a molecular mass of <120 kDa extravasate from experimental tumor neovasculature and may not be an accurate marker for measuring true blood volume fractions when in vivo imaging is performed in the steady state.

DOI10.1021/bc000091p
Alternate JournalBioconjug Chem
PubMed ID11312682
Related Institute: 
Molecular Imaging Innovations Institute (MI3)

Weill Cornell Medicine
Department of Radiology
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