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Molecular MR Imaging with Paramagnetic Perfluorocarbon Nanoparticles

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Nanoparticles in Biomedical Imaging

Part of the book series: Fundamental Biomedical Technologies ((FBMT,volume 102))

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Abstract

Targeted contrast agents, such as perfluorocarbon (PFC) nanoparticles, have been developed to allow conventional imaging modalities, including MRI, to detect and characterize specific pathological biomarkers of early disease rather than simply observe the anatomical manifestations occurring at very late stages. PFC nanoparticles are typically 200–300 nm in diameter and are encapsulated in a phospholipid shell, which provides an ideal surface for the incorporation of targeting ligands and/or imaging agents. Through chemical modification of the paramagnetic chelates incorporated on the particle surface, nanoparticle relaxivity as well as stability can be increased to improve the efficacy of MR molecular imaging. PFC nanoparticles can be targeted to a number of different biological epitopes, including fibrin, an abundant marker of ruptured atherosclerotic plaques; αvβ3-integrin, an endothelial biomarker of angiogenesis associated with atherosclerosis, tumor growth, and vascular injury; collagen III, a component of the extracellular matrix that is exposed after balloon angioplasty; and tissue factor, a vascular smooth muscle cell (VSMC) marker that is overexpressed following vascular injury. In addition to paramagnetic nanoparticles for 1H MRI, the PFC core has a high fluorine content that can be detected with 19F MRI, providing unambiguous and quantitative mapping of the contrast agent distribution. Another distinctive advantage of PFC nanoparticles for molecular imaging applications is their compatibility with several imaging modalities, including MRI, ultrasound, nuclear imaging, and CT.

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References

  • Ahrens, E.T., Feili-Hariri, M., Xu, H., Genove, G., Morel, P.A., 2003. Receptor-mediated endocytosis of iron-oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging. Magn Reson Med 49, 1006–1013.

    Article  PubMed  CAS  Google Scholar 

  • Ahrens, E.T., Flores, R., Xu, H., Morel, P.A., 2005. In vivo imaging platform for tracking immunotherapeutic cells. Nat Biotechnol 23, 983–987.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, S.A., Rader, R.K., Westlin, W.F., Null, C., Jackson, D., Lanza, G.M., Wickline, S.A., Kotyk, J.J., 2000. Magnetic resonance contrast enhancement of neovasculature with alpha(v)beta(3)-targeted nanoparticles. Magn Reson Med 44, 433–439.

    Article  PubMed  CAS  Google Scholar 

  • Banerjee, R., 2001. Liposomes: applications in medicine. J Biomater Appl 16, 3–21.

    Article  PubMed  CAS  Google Scholar 

  • Bishop, G.G., McPherson, J.A., Sanders, J.M., Hesselbacher, S.E., Feldman, M.J., McNamara, C.A., Gimple, L.W., Powers, E.R., Mousa, S.A., Sarembock, I.J., 2001. Selective alpha(v)beta(3)-receptor blockade reduces macrophage infiltration and restenosis after balloon angioplasty in the atherosclerotic rabbit. Circulation 103, 1906–1911.

    PubMed  CAS  Google Scholar 

  • Brooks, P.C., Stromblad, S., Klemke, R., Visscher, D., Sarkar, F.H., Cheresh, D.A., 1995. Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin. J Clin Invest 96, 1815–1822.

    Article  PubMed  CAS  Google Scholar 

  • Bulte, J.W., Arbab, A.S., Douglas, T., Frank, J.A., 2004. Preparation of magnetically labeled cells for cell tracking by magnetic resonance imaging. Methods Enzymol 386, 275–299.

    PubMed  CAS  Google Scholar 

  • Burnell, E.E., Cullis, P.R., de Kruijff, B., 1980. Effects of tumbling and lateral diffusion on phosphatidylcholine model membrane 31P-NMR lineshapes. Biochim Biophys Acta 603, 63–69.

    Article  PubMed  CAS  Google Scholar 

  • Caruthers, S.D., Neubauer, A.M., Hockett, F.D., Lamerichs, R., Winter, P.M., Scott, M.J., Gaffney, P.J., Wickline, S.A., Lanza, G.M., 2006. In vitro demonstration using 19F magnetic resonance to augment molecular imaging with paramagnetic perfluorocarbon nanoparticles at 1.5 Tesla. Invest Radiol 41, 305–312.

    Article  PubMed  Google Scholar 

  • Corjay, M.H., Diamond, S.M., Schlingmann, K.L., Gibbs, S.K., Stoltenborg, J.K., Racanelli, A.L., 1999. alphavbeta3, alphavbeta5, and osteopontin are coordinately upregulated at early time points in a rabbit model of neointima formation. J Cell Biochem 75, 492–504.

    Article  PubMed  CAS  Google Scholar 

  • Cyrus, T., Abendschein, D.R., Caruthers, S.D., Harris, T.D., Glattauer, V., Werkmeister, J.A., Ramshaw, J.A., Wickline, S.A., Lanza, G.M., 2006. MR three-dimensional molecular imaging of intramural biomarkers with targeted nanoparticles. J Cardiovasc Magn Reson 8, 535–541.

    Article  PubMed  Google Scholar 

  • Flacke, S., Fischer, S., Scott, M.J., Fuhrhop, R.J., Allen, J.S., McLean, M., Winter, P., Sicard, G.A., Gaffney, P.J., Wickline, S.A., Lanza, G.M., 2001. Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques. Circulation 104, 1280–1285.

    Article  PubMed  CAS  Google Scholar 

  • Flaim, S.F., 1994. Pharmacokinetics and side effects of perfluorocarbon-based blood substitutes. Artif Cells Blood Substit Immobil Biotechnol 22, 1043–1054.

    PubMed  CAS  Google Scholar 

  • Gossl, M., Malyar, N.M., Rosol, M., Beighley, P.E., Ritman, E.L., 2003a. Impact of coronary vasa vasorum functional structure on coronary vessel wall perfusion distribution. Am J Physiol Heart Circ Physiol 285, H2019–2026.

    CAS  Google Scholar 

  • Gossl, M., Rosol, M., Malyar, N.M., Fitzpatrick, L.A., Beighley, P.E., Zamir, M., Ritman, E.L., 2003b. Functional anatomy and hemodynamic characteristics of vasa vasorum in the walls of porcine coronary arteries. Anat Rec A Discov Mol Cell Evol Biol 272, 526–537.

    Article  Google Scholar 

  • Gossl, M., von Birgelen, C., Mintz, G.S., Bose, D., Eggebrecht, H., Baumgart, D., Haude, M., Erbel, R., 2003c. Volumetric assessment of ulcerated ruptured coronary plaques with three-dimensional intravascular ultrasound in vivo. Am J Cardiol 91, 992–996, A997.

    Article  Google Scholar 

  • Grant, C.W., Karlik, S., Florio, E., 1989. A liposomal MRI contrast agent: phosphatidylethanolamine-DTPA. Magn Reson Med 11, 236–243.

    Article  PubMed  CAS  Google Scholar 

  • Hall, C.S., Marsh, J.N., Scott, M.J., Gaffney, P.J., Wickline, S.A., Lanza, G.M., 2001. Temperature dependence of ultrasonic enhancement with a site-targeted contrast agent. J Acoust Soc Am 110, 1677–1684.

    Article  PubMed  CAS  Google Scholar 

  • Hamilton, M.C., Peek, G.J., Dux, A.E., 2005. Partial liquid ventilation. Pediatr Radiol 35, 1152–1156.

    Article  PubMed  Google Scholar 

  • Hu, G., Lijowski, M., Zhang, H., Partlow, K.C. Caruthers, S.D., Kiefer, G., Gulyas, G., Athey, P., Slott, M.J., Wickline, S.A., Lanza, G.M., 2007. Imaging of Vx-2 rabbit tumors with alpha(nu) beta3-integrin-targeted 111ln nanoparticles. Int. J. Cancer 120: 1951–1957.

    Article  PubMed  CAS  Google Scholar 

  • Jacobs, R.E., Fraser, S.E., 1994. Magnetic resonance microscopy of embryonic cell lineages and movements. Science 263, 681–684.

    Article  PubMed  CAS  Google Scholar 

  • Kerr, J.S., Mousa, S.A., Slee, A.M., 2001. Alpha(v)beta(3) integrin in angiogenesis and restenosis. Drug News Perspect 14, 143–150.

    PubMed  CAS  Google Scholar 

  • Khurana, R., Zhuang, Z., Bhardwaj, S., Murakami, M., De Muinck, E., Yla-Herttuala, S., Ferrara, N., Martin, J.F., Zachary, I., Simons, M., 2004. Angiogenesis-dependent and independent phases of intimal hyperplasia. Circulation 110, 2436–2443.

    Article  PubMed  Google Scholar 

  • Kircher, M.F., Allport, J.R., Graves, E.E., Love, V., Josephson, L., Lichtman, A.H., Weissleder, R., 2003. In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res 63, 6838–6846.

    PubMed  CAS  Google Scholar 

  • Kolodgie, F.D., Virmani, R., Burke, A.P., Farb, A., Weber, D.K., Kutys, R., Finn, A.V., Gold, H.K., 2004. Pathologic assessment of the vulnerable human coronary plaque. Heart 90, 1385–1391.

    Article  PubMed  CAS  Google Scholar 

  • Lanza, G.M., Abendschein, D.R., Hall, C.S., Marsh, J.N., Scott, M.J., Scherrer, D.E., Wickline, S.A., 2000a. Molecular imaging of stretch-induced tissue factor expression in carotid arteries with intravascular ultrasound. Invest Radiol 35, 227–234.

    Article  CAS  Google Scholar 

  • Lanza, G.M., Abendschein, D.R., Hall, C.S., Scott, M.J., Scherrer, D.E., Houseman, A., Miller, J.G., Wickline, S.A., 2000b. In vivo molecular imaging of stretch-induced tissue factor in carotid arteries with ligand-targeted nanoparticles. J Am Soc Echocardiogr 13, 608–614.

    Article  CAS  Google Scholar 

  • Lanza, G.M., Wallace, K.D., Scott, M.J., Cacheris, W.P., Abendschein, D.R., Christy, D.H., Sharkey, A.M., Miller, J.G., Gaffney, P.J., Wickline, S.A., 1996. A novel site-targeted ultrasonic contrast agent with broad biomedical application. Circulation 94, 3334–3340.

    PubMed  CAS  Google Scholar 

  • Laurent, S., Elst, L.V., Copoix, F., Muller, R.N., 2001. Stability of MRI paramagnetic contrast media: a proton relaxometric protocol for transmetallation assessment. Invest Radiol 36, 115–122.

    Article  PubMed  CAS  Google Scholar 

  • Marsh, J.N., Hall, C.S., Wickline, S.A., Lanza, G.M., 2002. Temperature dependence of acoustic impedance for specific fluorocarbon liquids. J Acoust Soc Am 112, 2858–2862.

    Article  PubMed  CAS  Google Scholar 

  • Mattrey, R.F., 1994. The potential role of perfluorochemicals (PFCs) in diagnostic imaging. Artif Cells Blood Substit Immobil Biotechnol 22, 295–313.

    PubMed  CAS  Google Scholar 

  • Mattrey, R.F., Long, D.C., 1988. Potential role of PFOB in diagnostic imaging. Invest Radiol 23 Suppl 1, S298–S301.

    PubMed  Google Scholar 

  • Modo, M., Mellodew, K., Cash, D., Fraser, S.E., Meade, T.J., Price, J., Williams, S.C., 2004. Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study. Neuroimage 21, 311–317.

    Article  PubMed  Google Scholar 

  • Morawski, A.M., Winter, P.M., Crowder, K.C., Caruthers, S.D., Fuhrhop, R.W., Scott, M.J., Robertson, J.D., Abendschein, D.R., Lanza, G.M., Wickline, S.A., 2004a. Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI. Magn Reson Med 51, 480–486.

    Article  CAS  Google Scholar 

  • Morawski, A.M., Winter, P.M., Yu, X., Fuhrhop, R.W., Scott, M.J., Hockett, F., Robertson, J.D., Gaffney, P.J., Lanza, G.M., Wickline, S.A., 2004b. Quantitative “magnetic resonance immunohistochemistry” with ligand-targeted (19)F nanoparticles. Magn Reson Med 52, 1255–1262.

    Article  CAS  Google Scholar 

  • Moreno, P.R., Purushothaman, K.R., Fuster, V., Echeverri, D., Truszczynska, H., Sharma, S.K., Badimon, J.J., O’Connor, W.N., 2004. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation 110, 2032–2038.

    Article  PubMed  Google Scholar 

  • Riess, J.G., 2005. Understanding the fundamentals of perfluorocarbons and perfluorocarbon emulsions relevant to in vivo oxygen delivery. Artif Cells Blood Substit Immobil Biotechnol 33, 47–63.

    Article  PubMed  CAS  Google Scholar 

  • Schmieder, A.H., Winter, P.M., Caruthers, S.D., Harris, T.D., Williams, T.A., Allen, J.S., Lacy, E.K., Zhang, H., Scott, M.J., Hu, G., Robertson, J.D., Wickline, S.A., Lanza, G.M., 2005. Molecular MR imaging of melanoma angiogenesis with alphanubeta3-targeted paramagnetic nanoparticles. Magn Reson Med 53, 621–627.

    Article  PubMed  CAS  Google Scholar 

  • Sharkey, R.M., Motta-Hennessy, C., Gansow, O.A., Brechbiel, M.W., Fand, I., Griffiths, G.L., Jones, A.L., Goldenberg, D.M., 1990. Selection of a DTPA chelate conjugate for monoclonal antibody targeting to a human colonic tumor in nude mice. Int J Cancer 46, 79–85.

    Article  PubMed  CAS  Google Scholar 

  • Sherry, A.D., Cacheris, W.P., Kuan, K.T., 1988. Stability constants for Gd3+ binding to model DTPA-conjugates and DTPA-proteins: implications for their use as magnetic resonance contrast agents. Magn Reson Med 8, 180–190.

    Article  PubMed  CAS  Google Scholar 

  • Sipkins, D.A., Cheresh, D.A., Kazemi, M.R., Nevin, L.M., Bednarski, M.D., Li, K.C., 1998. Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat Med 4, 623–626.

    Article  PubMed  CAS  Google Scholar 

  • Tenaglia, A.N., Peters, K.G., Sketch, M.H., Jr., Annex, B.H., 1998. Neovascularization in atherectomy specimens from patients with unstable angina: implications for pathogenesis of unstable angina. Am Heart J 135, 10–14.

    Article  PubMed  CAS  Google Scholar 

  • Thom, T., Haase, N., Rosamond, W., Howard, V.J., Rumsfeld, J., Manolio, T., Zheng, Z.J., Flegal, K., O’Donnell, C., Kittner, S., Lloyd-Jones, D., Goff, D.C., Jr., Hong, Y., Adams, R., Friday, G., Furie, K., Gorelick, P., Kissela, B., Marler, J., Meigs, J., Roger, V., Sidney, S., Sorlie, P., Steinberger, J., Wasserthiel-Smoller, S., Wilson, M., Wolf, P., 2006. Heart disease and stroke statistics–2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 113, e85–e151.

    Article  PubMed  Google Scholar 

  • Tilcock, C., Ahkong, Q.F., Koenig, S.H., Brown, R.D., 3rd, Davis, M., Kabalka, G., 1992. The design of liposomal paramagnetic MR agents: effect of vesicle size upon the relaxivity of surface-incorporated lipophilic chelates. Magn Reson Med 27, 44–51.

    Article  PubMed  CAS  Google Scholar 

  • Winter, P., Athey, P., Kiefer, G., Gulyas, G., Fuhrhop, R., Robertson, D., Wickline, S., Lanza, G., 2005a. Improved paramagnetic chelate for molecular imaging with MRI. J Magn Magn Mater 293, 540–545.

    Article  CAS  Google Scholar 

  • Winter, P.M., Caruthers, S.D., Kassner, A., Harris, T.D., Chinen, L.K., Allen, J.S., Lacy, E.K., Zhang, H., Robertson, J.D., Wickline, S.A., Lanza, G.M., 2003a. Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel alpha(nu)beta3targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer Res 63, 5838–5843.

    CAS  Google Scholar 

  • Winter, P.M., Caruthers, S.D., Yu, X., Song, S.K., Chen, J., Miller, B., Bulte, J.W., Robertson, J.D., Gaffney, P.J., Wickline, S.A., Lanza, G.M., 2003b. Improved molecular imaging contrast agent for detection of human thrombus. Magn Reson Med 50, 411–416.

    Article  CAS  Google Scholar 

  • Winter, P.M., Morawski, A.M., Caruthers, S.D., Fuhrhop, R.W., Zhang, H., Williams, T.A., Allen, J.S., Lacy, E.K., Robertson, J.D., Lanza, G.M., Wickline, S.A., 2003c. Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticles. Circulation 108, 2270–2274.

    Article  CAS  Google Scholar 

  • Winter, P.M., Shukla, H.P., Caruthers, S.D., Scott, M.J., Fuhrhop, R.W., Robertson, J.D., Gaffney, P.J., Wickline, S.A., Lanza, G.M., 2005b. Molecular imaging of human thrombus with computed tomography. Acad Radiol 12 Suppl 1, S9–S13.

    Article  Google Scholar 

  • Wood, M.L., Hardy, P.A., 1993. Proton relaxation enhancement. J Magn Reson Imaging 3, 149–156.

    Article  PubMed  CAS  Google Scholar 

  • Yeh, T.C., Zhang, W., Ildstad, S.T., Ho, C., 1993. Intracellular labeling of T-cells with superparamagnetic contrast agents. Magn Reson Med 30, 617–625.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Patrick M. Winter
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  2. Shelton D. Caruthers
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  3. Anne H. Schmieder
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  4. Anne M. Neubauer
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  5. Gregory M. Lanza
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  6. Samuel A. Wickline
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Editor information

Editors and Affiliations

  1. Department of Radiology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, 21205

    Jeff W.M. Bulte

  2. Institute of Psychiatry King’s College London, Center for the Cellular Basis of Behaviour, 125 Coldharbour Lane, London SE5 9NU, United Kingdom

    Michel M.J. Modo

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Winter, P.M., Caruthers, S.D., Schmieder, A.H., Neubauer, A.M., Lanza, G.M., Wickline, S.A. (2008). Molecular MR Imaging with Paramagnetic Perfluorocarbon Nanoparticles. In: Bulte, J.W., Modo, M.M. (eds) Nanoparticles in Biomedical Imaging. Fundamental Biomedical Technologies, vol 102. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72027-2_8

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