In vivo angiogenesis imaging of solid tumors by alpha(v)beta(3)-targeted, dual-modality micellar nanoprobes.

Abstract

The objective of this study was to develop and evaluate an alpha(v)beta(3)-specific nanoprobe consisting of fluorescent superparamagnetic polymeric micelles (FSPPM) for in vivo imaging of tumor angiogenesis. Spherical micelles were produced using poly(ethylene glycol)-b-poly(d,l-lactide) co-polymers conjugated with tetramethylrhodamine, a fluorescent dye, and loaded with superparamagnetic iron oxide nanoparticles. The resulting micelle diameter was 50-70 nm by dynamic light scattering and transmission electron microscopy measurements. Micelles were encoded with an alpha(v)beta(3)-specific peptide, cyclic RGDfK, and optimized for maximum fluorescence and targeting in alpha(v)beta(3)-overexpressing cells in vitro. In mice, cRGD-FSPPM-treated animals showed alpha(v)beta(3)-specific FSPPM accumulation in human lung cancer subcutaneous tumor xenografts. Together with the histological validation, the three-dimensional gradient echo magnetic resonance imaging (MRI) data provide high spatial resolution mapping and quantification of angiogenic vasculature in an animal tumor model using targeted, ultrasensitive MRI nanoprobes.

• Authors: Chase W Kessinger, Chalermchai Khemtong, Osamu Togao, Masaya Takahashi, Baran D Sumer, Jinming Gao
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 235 Issue 8 Pg. 957-65 (Aug 2010) ISSN: 1535-3699 [Electronic] England
• PMID: 20660096 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorescent Dyes
• Integrin alphaVbeta3
• Micelles
• Peptides, Cyclic
• Polyesters
• Rhodamines
• cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl)
• poly(lactide)
• tetramethylrhodamine
• Ferrosoferric Oxide

Topics

• Animals
• Female
• Ferrosoferric Oxide (chemistry)
• Fluorescent Dyes (analysis, chemistry)
• Humans
• Integrin alphaVbeta3 (metabolism)
• Lung Neoplasms (blood supply, metabolism)
• Magnetic Resonance Imaging (methods)
• Magnetics
• Metal Nanoparticles (analysis)
• Mice
• Mice, Nude
• Micelles
• Microscopy, Electron, Transmission
• Molecular Imaging (methods)
• Neoplasms (blood supply, metabolism)
• Neovascularization, Pathologic (diagnosis)
• Peptides, Cyclic (metabolism)
• Polyesters (chemical synthesis, chemistry)
• Rhodamines (analysis, chemistry)
• Scattering, Radiation
• Xenograft Model Antitumor Assays