Targeted multifunctional multimodal protein-shell microspheres as cancer imaging contrast agents

Renu John, Freddy T. Nguyen, Kenneth J. Kolbeck, Eric J. Chaney, Marina Marjanovic, Kenneth S. Suslick, Stephen A. Boppart

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Purpose: In this study, protein-shell microspheres filled with a suspension of iron oxide nanoparticles in oil are demonstrated as multimodal contrast agents in magnetic resonance imaging (MRI), magnetomotive optical coherence tomography (MM-OCT), and ultrasound imaging. The development, characterization, and use of multifunctional multimodal microspheres are described for targeted contrast and therapeutic applications. Procedures: A preclinical rat model was used to demonstrate the feasibility of the multimodal multifunctional microspheres as contrast agents in ultrasound, MM-OCT and MRI. Microspheres were functionalized with the RGD peptide ligand, which is targeted to α vβ 3 integrin receptors that are over-expressed in tumors and atherosclerotic lesions. Results: These microspheres, which contain iron oxide nanoparticles in their cores, can be modulated externally using a magnetic field to create dynamic contrast in MM-OCT. With the presence of iron oxide nanoparticles, these agents also show significant negative T2 contrast in MRI. Using ultrasound B-mode imaging at a frequency of 30 MHz, a marked enhancement of scatter intensity from in vivo rat mammary tumor tissue was observed for these targeted protein microspheres. Conclusions: Preliminary results demonstrate multimodal contrast-enhanced imaging of these functionalized microsphere agents with MRI, MM-OCT, ultrasound imaging, and fluorescence microscopy, including in vivo tracking of the dynamics of these microspheres in real-time using a high-frequency ultrasound imaging system. These targeted oil-filled protein microspheres with the capacity for high drug-delivery loads offer the potential for local delivery of lipophilic drugs under image guidance.

Original languageEnglish (US)
Pages (from-to)17-24
Number of pages8
JournalMolecular Imaging and Biology
Volume14
Issue number1
DOIs
StatePublished - Feb 1 2012

Keywords

  • Alpha(v) beta(3) targeting
  • Contrast agents
  • Iron oxide
  • Magnetic resonance imaging
  • Magnetomotive optical coherence tomography
  • Protein microspheres
  • RGD peptide
  • Ultrasound imaging

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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