Targeted Multifunctional Multimodal Protein-Shell Microspheres as Cancer Imaging Contrast Agents

• DOI: 10.1007/s11307-011-0473-7
• Publication Date: 2011-02-04T18:50:22Z
• Authors: Renu John; Freddy T. Nguyen; Kenneth J. Kolbeck; Eric J. Chaney; Marina Marjanovic; Kenneth S. Suslick; Stephen A. Boppart
• Keywords: Diagnostic Imaging; Microbubbles; Contrast Media; Mammary Neoplasms, Experimental; 02 engineering and technology; Integrin alphaVbeta3; Microspheres; Rats; 3. Good health; Rats, Sprague-Dawley; Animals; Feasibility Studies; Female; Magnetite Nanoparticles; 0210 nano-technology; Oligopeptides; Ultrasonography

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.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(v)β₃ integrin receptors that are over-expressed in tumors and atherosclerotic lesions.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.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.