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

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

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 2012
Externally publishedYes

Fingerprint

Microspheres
Contrast Media
Optical Coherence Tomography
Neoplasms
Proteins
Magnetic Resonance Imaging
Nanoparticles
Ultrasonography
Oils
Magnetic Fields
Fluorescence Microscopy
Integrins
Pharmaceutical Preparations
Suspensions
Breast Neoplasms
Ligands

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

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Targeted multifunctional multimodal protein-shell microspheres as cancer imaging contrast agents. / John, Renu; Nguyen, Freddy T.; Kolbeck, Kenneth; Chaney, Eric J.; Marjanovic, Marina; Suslick, Kenneth S.; Boppart, Stephen A.

In: Molecular Imaging and Biology, Vol. 14, No. 1, 02.2012, p. 17-24.

Research output: Contribution to journalArticle

John, Renu ; Nguyen, Freddy T. ; Kolbeck, Kenneth ; Chaney, Eric J. ; Marjanovic, Marina ; Suslick, Kenneth S. ; Boppart, Stephen A. / Targeted multifunctional multimodal protein-shell microspheres as cancer imaging contrast agents. In: Molecular Imaging and Biology. 2012 ; Vol. 14, No. 1. pp. 17-24.
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