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

Exp Biol Med (Maywood). 2010 Aug;235(8):957-65. doi: 10.1258/ebm.2010.010096.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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