Molecular MR imaging of melanoma angiogenesis with α νβ3-targeted paramagnetic nanoparticles

Anne H. Schmieder, Patrick M. Winter, Shelton D. Caruthers, Thomas D. Harris, Todd A. Williams, John S. Allen, Elizabeth K. Lacy, Huiying Zhang, Michael J. Scott, Grace Hu, J. David Robertson, Samuel A. Wickline, Gregory M. Lanza

Research output: Contribution to journalArticlepeer-review

228 Scopus citations

Abstract

Neovascularization is a critical component in the progression of malignant melanoma. The objective of this study was to determine whether ανβ3-targeted paramagnetic nanoparticles can detect and characterize sparse ανβ integrin expression on neovasculature induced by nascent melanoma xenografts (∼30 mm 3) at 1.5T. Athymic nude mice bearing human melanoma tumors were intravenously injected with ανβ3-integrin- targeted paramagnetic nanoparticles, nontargeted paramagnetic nanoparticles, or ανβ3-targeted nonparamagnetic nanoparticles 2 hr before they were injected with ανβ3- integrin-targeted paramagnetic nanoparticles (i.e., in vivo competitive blockade) and imaged with MRI. Contrast enhancement of neovascularity in animals that received ανβ3-targeted paramagnetic nanoparticles increased 173% by 120 min. Signal contrast with nontargeted paramagnetic nanoparticles was approximately 50% less than that in the targeted group (P < 0.05). Molecular MRI results were corroborated by histology. In a competitive cell adhesion assay, incubation of ανβ 3-expressing cells with targeted nanoparticles significantly inhibited binding to a vitronectin-coated surface, confirming the bioactivity of the targeted nanoparticles. The present study lowers the limit previously reported for detecting sparse biomarkers with molecular MRI in vivo. This technique may be employed to noninvasively detect very small regions of angiogenesis associated with nascent melanoma tumors, and to phenotype and stage early melanoma in a clinical setting.

Original languageEnglish
Pages (from-to)621-627
Number of pages7
JournalMagnetic resonance in medicine
Volume53
Issue number3
DOIs
StatePublished - Mar 2005

Keywords

  • Angiogenesis
  • Magnetic resonance
  • Melanoma
  • Molecular imaging
  • Targeted contrast agent

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