PMID: 11312682Apr 21, 2001Paper

Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging

Bioconjugate Chemistry
R WeisslederH J Weinmann

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 differe...Continue Reading

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Citations

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