In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes
Edited by Erich P. Ippen, Massachusetts Institute of Technology, Cambridge, MA, and approved February 26, 2010 (received for review December 1, 2009)
Abstract
Dynamic magnetomotion of magnetic nanoparticles (MNPs) detected with magnetomotive optical coherence tomography (MM-OCT) represents a new methodology for contrast enhancement and therapeutic interventions in molecular imaging. In this study, we demonstrate in vivo imaging of dynamic functionalized iron oxide MNPs using MM-OCT in a preclinical mammary tumor model. Using targeted MNPs, in vivo MM-OCT images exhibit strong magnetomotive signals in mammary tumor, and no significant signals were measured from tumors of rats injected with nontargeted MNPs or saline. The results of in vivo MM-OCT are validated by MRI, ex vivo MM-OCT, Prussian blue staining of histological sections, and immunohistochemical analysis of excised tumors and internal organs. The MNPs are antibody functionalized to target the human epidermal growth factor receptor 2 (HER2 neu) protein. Fc-directed conjugation of the antibody to the MNPs aids in reducing uptake by macrophages in the reticulo-endothelial system, thereby increasing the circulation time in the blood. These engineered magnetic nanoprobes have multifunctional capabilities enabling them to be used as dynamic contrast agents in MM-OCT and MRI.
Acknowledgments.
We thank Boris Odintsov from the Biomedical Imaging Center (BIC) at the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, for the fabrication of the rf coil for in vivo MRI studies, the research personnel at BIC for technical support, and Scott Robinson from the Imaging Technology Group at the Beckman Institute for Advanced Science and Technology for his assistance with TEM analysis. This research was supported in part by grants from the National Institutes of Health (Roadmap Initiative, NIBIB, R21 EB005321; NIBIB, R01 EB005221; NIBIB, R01 EB009073; and NCI RC1 CA147096, S.A.B.).
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References
1
EE Graves, R Weissleder, V Ntziachristos, Fluorescence molecular imaging of small animal tumor models. Curr Mol Med 4, 419–430 (2004).
2
JWM Bulte, DL Kraitchman, Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17, 484–494 (2004).
3
J Liu, et al., Nanoparticles as image enhancing agents for ultrasonography. Phys Med Biol 51, 2179–2189 (2006).
4
LV Wang, Multiscale photoacoustic microscopy and computed tomography. Nat Photonics 3, 503–509 (2009).
5
GD Luker, D Piwnica-Worms, Molecular imaging in vivo with PET and SPECT. Acad Radiol 8, 4–14 (2001).
6
SA Boppart, AL Oldenburg, C Xu, DL Marks, Optical probes and techniques for molecular contrast enhancement in coherence imaging. J Biomed Opt 10, 041208 (2005).
7
D Huang, et al., Optical coherence tomography. Science 254, 1178–1181 (1991).
8
JG Fujimoto, et al., Optical biopsy and imaging using optical coherence tomography. Nat Med 1, 970–972 (1995).
9
AL Oldenburg, JR Gunther, SA Boppart, Imaging magnetically labeled cells with magnetomotive optical coherence tomography. Opt Lett 30, 747–749 (2005).
10
AL Oldenburg, FJ Toublan, KS Suslick, A Wei, SA Boppart, Magnetomotive contrast for in vivo optical coherence tomography. Opt Express 13, 6597–6614 (2005).
11
AL Oldenburg, V Crecea, SA Rinne, SA Boppart, Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues. Opt Express 16, 11525–11539 (2008).
12
KD Rao, M Choma, S Yazdanfar, AM Rollins, JA Izatt, Molecular contrast in optical coherence tomography using a pump-probe technique. Opt Lett 28, 340–342 (2003).
13
DC Adler, S-W Huang, R Huber, JG Fujimoto, Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography. Opt Express 16, 4376–4393 (2008).
14
MC Skala, MJ Crow, A Wax, JA Izatt, Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres. Nano Lett 8, 3461–3467 (2008).
15
W Liu, JA Frank, Detection and quantification of magnetically labeled cells by cellular MRI. Eur J Radiol 70, 258–264 (2009).
16
V Crecea, AL Oldenburg, X Liang, TS Ralston, SA Boppart, Magnetomotive nanoparticle transducers for optical rheology of viscoeleastic materials. Opt Express 17, 23114–23122 (2009).
17
XH Gao, et al., In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22, 969–976 (2004).
18
C Loo, A Lowery, N Halas, J West, R Drezek, Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett 5, 709–711 (2005).
19
NW Shi Kam, M O'Connell, JA Wisdom, H Dai, Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc Natl Acad Sci USA 102, 11600–11605 (2005).
20
K Sokolov, et al., Real-time vital optical imaging of precancer using anti-epidermal growth factor receptor antibodies conjugated to gold nanoparticles. Cancer Res 63, 1999–2004 (2003).
21
P Sharma, et al., Gd nanoparticulates: From magnetic resonance imaging to neutron capture therapy. Adv Powder Technol 18, 663–698 (2007).
22
K Lind, M Kresse, NP Debus, RH Muller, A novel formulation for superparamagnetic iron oxide particles enhancing MR lymphography: Comparison of physicochemical properties and the in vivo behaviour. J Drug Target 10, 221–230 (2002).
23
N Nasongkla, et al., Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett 6, 2427–2430 (2006).
24
TM Lee, et al., Engineered microsphere contrast agents for optical coherence tomography. Opt Lett 28, 1546–1548 (2003).
25
H Lee, et al., Antibiofouling polymer-coated superparamagnetic iron oxide nanoparticles as potential magnetic resonance contrast agents for in vivo cancer imaging. J Am Chem Soc 128, 7383–7389 (2006).
26
AK Gupta, M Gupta, Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26, 3995–4021 (2005).
27
MA Funovics, et al., MR imaging of the her2/neu and 9.2.27 tumor antigens using immunospecific contrast agents. Magn Reson Imaging 22, 843–850 (2004).
28
D Artemov, N Mori, R Ravi, ZM Bhujwalla, Magnetic resonance molecular imaging of the HER-2/neu receptor. Cancer Res 63, 2723–2727 (2003).
29
JR McCarthy, R Weissleder, Multifunctional magnetic nanoparticles for targeted imaging and therapy. Adv Drug Deliver Rev 60, 1241–1251 (2008).
30
SJ DeNardo, et al., Development of tumor targeting bioprobes (in-chimeric L6 monoclonal antibody nanoparticles) for alternating magnetic field cancer therapy. Clin Cancer Res 11, 7087s–7092s (2005).
31
R Rezaeipoor, et al., Fc-directed antibody conjugation of magnetic nanoparticles for enhanced molecular targeting. J Innov Opt Health Sciences 2, 387–396 (2009).
32
RL Camp, M Dolled-Filhar, L King Bonnie, DL Rimm, Quantitative analysis of breast cancer tissue microarrays shows that both high and normal levels of HER2 expression are associated with poor outcome. Cancer Res 63, 1445–1448 (2003).
33
MA Choma, AK Ellerbee, C Yang, TL Creazzo, JA Izatt, Spectral domain phase microscopy. Opt Lett 30, 1162–1164 (2005).
34
R Rezaeipoor, EJ Chaney, AL Oldenburg, SA Boppart, Expression order of alpha-v and beta-3 integrin subunits in the N-methyl-N-nitrosourea-induced rat mammary tumor model. Cancer Invest 27, 496–503 (2009).
35
FT Nguyen, et al., Intraoperative evaluation of breast tumor margins with optical coherence tomography. Cancer Res 69, 8790–8796 (2009).
36
H-L Duan, Z-Q Shen, X-W Wang, F-H Chao, J-W Li, Preparation of immunomagnetic iron-dextran nanoparticles and application in rapid isolation of E.coli 0157:H7 from foods. World J Gastroentero 11, 3660–3664 (2005).
37
T Shen, R Weissleder, M Papisov, A Bogdanov, TJ Brady, Monocrystalline iron oxide nanocompounds (MION): Physicochemical properties. Magn Reson Med 29, 599–604 (1993).
38
C Grüttner, et al., Synthesis and antibody conjugation of magnetic nanoparticles with improved specific power absorption rates for alternating magnetic field cancer therapy. J Magn Magn Mater 311, 181–186 (2007).
39
LX Tiefenauer, G Kühne, RY Andres, Antibody-magnetite nanoparticles: In vitro characterization of a potential tumor-specific contrast agent for magnetic resonance imaging. Bioconjugate Chem 4, 347–352 (1993).
40
E Okon, et al., Biodegradation of magnetite dextran nanoparticles in the rat: A histologic and biophysical study. Lab Invest 71, 895–903 (1994).
41
F Bonneaux, E Dellacherie, P Labrude, C Vigneron, Hemoglobin-dialdehyde dextran conjugates: Improvement of their oxygen-binding properties with anionic groups. J Protein Chem 15, 461–465 (1996).
42
MB Wilson, PK Nakane, The covalent coupling of proteins to periodate-oxidized sephadex: A new approach to immunoadsorbent preparation. J Immunol Methods 12, 171–181 (1976).
43
X Wang, L Yang, Z Chen, DM Shin, Application of nanotechnology to cancer therapy and imaging. CA-Cancer J Clin 58, 97–110 (2008).
44
SM Moghimi, AC Hunter, JC Murray, Nanomedicine: Current status and future prospects. FASEB J 19, 311–330 (2005).
45
YXJ Wang, SM Hussain, GP Krestin, Superparamagnetic iron oxide contrast agents: Physicochemical characteristics and applications in MR imaging. Eur Radiol 11, 2319–2331 (2001).
46
WJ Gullick, et al., Expression of the c-erbB-2 protein in normal and transformed cells. Int J Cancer 15, 246–254 (1987).
47
R John, EJ Chaney, SA Boppart, Dynamics of magnetic nanoparticle-based contrast agents in tissues tracked using magnetomotive optical coherence tomography. IEEE J Sel Top Quant Electron: Biophotonics, 10.1109/JSTQE.2009.2029547. (2009).
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Published online: April 19, 2010
Published in issue: May 4, 2010
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Acknowledgments
We thank Boris Odintsov from the Biomedical Imaging Center (BIC) at the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, for the fabrication of the rf coil for in vivo MRI studies, the research personnel at BIC for technical support, and Scott Robinson from the Imaging Technology Group at the Beckman Institute for Advanced Science and Technology for his assistance with TEM analysis. This research was supported in part by grants from the National Institutes of Health (Roadmap Initiative, NIBIB, R21 EB005321; NIBIB, R01 EB005221; NIBIB, R01 EB009073; and NCI RC1 CA147096, S.A.B.).
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This article is a PNAS Direct Submission.
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The authors declare no conflict of interest.
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In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes, Proc. Natl. Acad. Sci. U.S.A.
107 (18) 8085-8090,
https://doi.org/10.1073/pnas.0913679107
(2010).
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