TY - JOUR
T1 - Targeted multifunctional multimodal protein-shell microspheres as cancer imaging contrast agents
AU - John, Renu
AU - Nguyen, Freddy T.
AU - Kolbeck, Kenneth J.
AU - Chaney, Eric J.
AU - Marjanovic, Marina
AU - Suslick, Kenneth S.
AU - Boppart, Stephen A.
N1 - Funding Information:
Acknowledgements. This research was supported in part by grants from the National Institutes of Health (Roadmap Initiative, NIBIB R21 EB005321, NIBIB R01 EB009073, and NCI RC1 CA147096).
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - Alpha(v) beta(3) targeting
KW - Contrast agents
KW - Iron oxide
KW - Magnetic resonance imaging
KW - Magnetomotive optical coherence tomography
KW - Protein microspheres
KW - RGD peptide
KW - Ultrasound imaging
UR - http://www.scopus.com/inward/record.url?scp=84861478435&partnerID=8YFLogxK
U2 - 10.1007/s11307-011-0473-7
DO - 10.1007/s11307-011-0473-7
M3 - Article
C2 - 21298354
AN - SCOPUS:84861478435
SN - 1536-1632
VL - 14
SP - 17
EP - 24
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 1
ER -