Journal of Nuclear Cardiology

, Volume 11, Issue 6, pp 733–743 | Cite as

Magnetic resonance molecular imaging with nanoparticles

  • Gregory M. Lanza
  • Patrick M. Winter
  • Shelton D. Caruthers
  • Anne M. Morawski
  • Anne H. Schmieder
  • Katherine C. Crowder
  • Samuel A. Wickline
From bench to imaging

Abstract

Molecular imaging agents are extending the potential of noninvasive medical diagnosis from basic gross anatomic descriptions to complicated phenotypic characterizations based on the recognition of unique cell surface biochemical signatures. Although originally the purview of nuclear medicine, molecular imaging is now a prominent feature of most clinically relevant imaging modalities, in particular magnetic resonance (MR) imaging. MR nanoparticulate agents afford the opportunity not only for targeted diagnostic studies but also for image-monitored site-specific therapeutic delivery, much like the “magic bullet” envisioned by Paul Erhlich 100 years ago. Combining high-resolution MR molecular imaging with drug delivery will facilitate verification and quantification of treatment (ie, rational targeted therapy) and will offer new clinical approaches to many diseases.

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References

  1. 1.
    GutierrezF, BrownJ, MirowitzS. Cardiovascular magnetic resonance imaging. St Louis:Mosby; 1992.Google Scholar
  2. 2.
    Nelson KL, Runge VM. Basic principles of MR contrast. Top Magn Reson Imaging 1995;7:124–36.PubMedCrossRefGoogle Scholar
  3. 3.
    Moghimi S, Patel H. Serum opsonins and phagocytosis of saturated and unsaturated phospholipid liposomes. Biochim Biophys Acta 1989;984:384–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Babes L, Denizot B, Tanguy G, Le Jeune JJ, Jallet P. Synthesis of iron oxide nanoparticles used as MRI contrast agents: a parametric study. J Colloid Interface Sci 1999;212:474–82.PubMedCrossRefGoogle Scholar
  5. 5.
    Berry I, Benderbous S, Ranjeva JP, Gracia-Meavilla D, Manelfe C, Le Bihan D. Contribution of Sinerem used as blood-pool contrast agent: detection of cerebral blood volume changes during apnea in the rabbit. Magn Reson Med 1996;36:415–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Van Gansbeke D, Matos C, Metens T. Vascular enhancement with superparamagnetic iron oxide. AJR Am J Roentgenol 1996; 167:813–4.PubMedGoogle Scholar
  7. 7.
    Stillman AE, Wilke N, Li D, Haacke M, McLachlan S. Ultrasmail superparamagnetic iron oxide to enhance MRA of the renal and coronary arteries: studies in human patients. J Comput Assist Tomogr 1996;20:51–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Anzai Y, Rince MR, Chenevert TL, Maki JH, Londy F, London M, et al. MR angiography with an ultrasmall superparamagnetic iron oxide blood pool agent. J Magn Reson Imaging 1997;7:209–14.PubMedCrossRefGoogle Scholar
  9. 9.
    Loubeyre P, Zhao S, Canet E, Abidi H, Benderbous S, Revel D. Ultrasmall superparamagnetic iron oxide particles (AMI 227) as a blood pool contrast agent for MR angiography: experimental study in rabbits. J Magn Reson Imaging 1997;7:958–62.PubMedCrossRefGoogle Scholar
  10. 10.
    Moore A, Marecos E, Bogdanov A Jr, Weissleder R. Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model. Radiology 2000;214:568–74.PubMedGoogle Scholar
  11. 11.
    Semelka RC, Lee JK, Worawattanakul S, Noone TC, Patt RH, Ascher SM. Sequential use of ferumoxide particles and gadolinium chelate for the evaluation of focal liver lesions on MRI. J Magn Reson Imaging 1998;8:670–4.PubMedCrossRefGoogle Scholar
  12. 12.
    Scott J, Ward J, Guthrie JA, Wilson D, Robinson PJ. MRI of liver: a comparison of CNR enhancement using high dose and low dose ferumoxide infusion in patients with colorectal liver metastases. Magn Reson Imaging 2000;18:297–303.PubMedCrossRefGoogle Scholar
  13. 13.
    Nakayama M, Yamashita Y, Mitsuzaki K, Yi T, Arakawa A, Katahira K, et al. Improved tissue characterization of focal liver lesions with ferumoxide-enhanced Tl and T2-weighted MR imaging. J Magn Reson Imaging 2000; 11:647–54.PubMedCrossRefGoogle Scholar
  14. 14.
    Imam K, Bluemke DA. MR imaging in the evaluation of hepatic metastases. Magn Reson Imaging Clin N Am 2000;8:741–56.PubMedGoogle Scholar
  15. 15.
    Kato H, Kanematsu M, Kondo H, Goshima S, Matsuo M, Hoshi H, et al. Ferumoxide-enhanced MR imaging of hepatocellular carcinoma: correlation with histologic tumor grade and tumor vascularity. J Magn Reson Imaging 2004; 19:76–81.PubMedCrossRefGoogle Scholar
  16. 16.
    Araki T. SPIO-MRI in the detection of hepatocellular carcinoma. J Gastroenterol 2000;35:874–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Nakamura H, Ito N, Kotake F, Mizokami Y, Matsuoka T. Tumor-detecting capacity and clinical usefulness of SPIO-MRI in patients with hepatocellular carcinoma. J Gastroenterol 2000;35:849–55.PubMedCrossRefGoogle Scholar
  18. 18.
    Stiskal M, Schwickert HC, Demsar F, Roberts TP, Szolar D, Weissleder R, et al. Contrast enhancement in experimental radiation-induced liver injury: comparison of hepatocellular and reticu-loendothelial particulate contrast agents. J Magn Reson Imaging 1996;6:286–90.PubMedCrossRefGoogle Scholar
  19. 19.
    Weissleder R, Reimer P, Lee AS, Wittenberg J, Brady TJ. MR receptor imaging: ultrasmall iron oxide particles targeted to asia-loglycoprotein receptors. AJR Am J Roentgenol 1990;155:1161–7.PubMedGoogle Scholar
  20. 20.
    Reimer P, Weissleder R, Brady TJ, Yeager AE, Baldwin BH, Tennant BC, et al. Experimental hepatocellular carcinoma: MR receptor imaging. Radiology 1991;180:641–5.PubMedGoogle Scholar
  21. 21.
    Weissleder R, Elizondo G, Wittenberg J, Lee AS, Josephson L, Brady TJ. Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging. Radiology 1990;175:494–8.PubMedGoogle Scholar
  22. 22.
    Nguyen BC, Stanford W, Thompson BH, Rossi NP, Kemstine KH, Kem JA, et al. Multicenter clinical trial of ultrasmall superparamagnetic iron oxide in the evaluation of mediastinal lymph nodes in patients with primary lung carcinoma. J Magn Reson Imaging 1999;10:468–73.PubMedCrossRefGoogle Scholar
  23. 23.
    Harisinghani MG, Barentsz J, Hahn PF, Desemo WM, Tabatabaei S, van de Kaa CH, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003; 348:2491–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Vassallo P, Matei C, Heston WD, McLachlan SJ, Koutcher JA, Castellino RA. AMI-227-enhanced MR lymphography: usefulness for differentiating reactive from tumor-bearing lymph nodes. Radiology 1994;193:501–6.PubMedGoogle Scholar
  25. 25.
    Vassallo P, Matei C, Heston WD, McLachlan SJ, Koutcher JA, Castellino RA. Characterization of reactive versus tumor-bearing lymph nodes with interstitial magnetic resonance lymphography in an animal model. Invest Radiol 1995;30:706–11.PubMedCrossRefGoogle Scholar
  26. 26.
    Rety F, Clement O, Siauve N, Cuenod CA, Camot F, Sich M, et al. MR lymphography using iron oxide nanoparticles in rats: pharma-cokinetics in the lymphatic system after intravenous injection. J Magn Reson Imaging 2000; 12:734–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Torchia MG, Nason R, Danzinger R, Lewis JM, Thliveris JA. Interstitial MR lymphangiography for the detection of sentinel lymph nodes. J Surg Oncol 2001;78:151–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Harisinghani MG, Dixon WT, Saksena MA, Brachtel E, Blezek DJ, Dhawale PJ, et al. MR lymphangiography: imaging strategies to optimize the imaging of lymph nodes with ferumoxtran-10. Radiographies 2004;24:867–78.CrossRefGoogle Scholar
  29. 29.
    Bulte JW, de Jonge MW, Kamman RL, Zuiderveen F, The TH, de Leij L, et al. Magnetite as a potent contrast-enhancing agent in magnetic resonance imaging to visualize blood-brain barrier disruption. Acta Neurochir Suppl (Wien) 1993;57:30–4.Google Scholar
  30. 30.
    Schulze E, Ferrucci JT Jr, Poss K, Lapointe L, Bogdanova A, Weissleder R. Cellular uptake and trafficking of a prototypical magnetic iron oxide label in vitro. Invest Radiol 1995;30:604–10.PubMedCrossRefGoogle Scholar
  31. 31.
    Moore A, Weissleder R, Bogdanov A Jr. Uptake of dextran-coated monocrystalline iron oxides in tumor cells and macrophages. J Magn Reson Imaging 1997;7:1140–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Ruehm SG, Corot C, Vogt P, Cristina H, Debatin JF. Ultrasmall superparamagnetic iron oxide-enhanced MR imaging of atherosclerotic plaque in hyperlipidemic rabbits. Acad Radiol 2002; 9(Suppl l):S143–4.Google Scholar
  33. 33.
    Kooi ME, Cappendijk VC, Cleutjens KB, Kessels AG, Kitslaar PJ, Borgers M, et al. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation 2003;107:2453–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Kanno S, Wu Y, Lee P, Dodd S, Williams M, Griffith B, et al. Macrophage accumulation associated with rat cardiac allograft rejection detected by magnetic resonance imaging with ultrasmall superparamagnetic iron oxide particles. Circulation 2001; 104:934–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Bulte JW, Zhang S, van Gelderen P, Herynek V, Jordan EK, Duncan ID, et al. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci U S A 1999;96:15256–61.PubMedCrossRefGoogle Scholar
  36. 36.
    Bulte J, Douglas T, Witwer B, Zhang S, Lewis B, van Gelderen P, et al. Monitoring stem cell therapy in vivo using magnetodendrimers as a new class of cellular MR contrast agents. Acad Radiol 2002;9(Suppl 2):S332–5.CrossRefGoogle Scholar
  37. 37.
    Frank JA, Miller BR, Arbab AS, Zywicke HA, Jordan EK, Lewis BK, et al. Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology 2003;228:480–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Wilhelm C, Billotey C, Roger J, Pons JN, Bacri JC, Gazeau F. Intracellular uptake of anionic superparamagnetic nanoparticles as a function of their surface coating. Biomaterials 2003;24:1001–11.PubMedCrossRefGoogle Scholar
  39. 39.
    Anderson SA, Glod J, Arbab AS, Noel M, Ashari P, Fine HA, et al. Non-invasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model. Blood 2004. (prepublished online August 26, 2004; DOI 10.1182/Blood-2004-06-2222)Google Scholar
  40. 40.
    Lewin M, Carlesso N, Tung CH, Tang XW, Cory D, Scadden DT, et al. Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 2000; 18:410–44.PubMedCrossRefGoogle Scholar
  41. 41.
    Josephson L, Tung CH, Moore A, Weissleder R. High efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. Bioconjug Chem 1999;10:186–91.PubMedCrossRefGoogle Scholar
  42. 42.
    Allport JR, Weissleder R. In vivo imaging of gene and cell therapies. Exp Hematol 2001;29:1237–46.PubMedCrossRefGoogle Scholar
  43. 43.
    Wunderbaldinger P, Josephson L, Weissleder R. Tat peptide directs enhanced clearance and hepatic permeability of magnetic nanoparticles. Bioconjug Chem 2002; 13:264–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Moore A, Grimm J, Han B, Santamaria P. Tracking the recruitment of diabetogenic CD8+ T-cells to the pancreas in real time. Diabetes 2004;53:1459–66.PubMedCrossRefGoogle Scholar
  45. 45.
    Weissleder R, Lee AS, Khaw BA, Shen T, Brady TJ. Antimyosin-labeled monocrystalline iron oxide allows detection of myocardial infarct: MR antibody imaging. Radiology 1992;182:381–5.PubMedGoogle Scholar
  46. 46.
    Dodd CH, Hsu HC, Chu WJ, Yang P, Zhang HG, Mountz JD Jr, et al. Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles. J Immunol Methods 2001 ;256:89–105.PubMedCrossRefGoogle Scholar
  47. 47.
    Kang HW, Josephson L, Petrovsky A, Weissleder R, Bogdanov A Jr. Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture. Bioconjug Chem 2002; 13:122–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Schellenberger EA, Bogdanov A Jr, Hogemann D, Tait J, Weissleder R, Josephson L. Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI. Mol Imaging 2002;l:102–7.CrossRefGoogle Scholar
  49. 49.
    Johansson LO, Bjomerud A, Ahlstrom HK, Ladd DL, Fujii DK. A targeted contrast agent for magnetic resonance imaging of thrombus: implications of spatial resolution. J Magn Reson Imaging 2001;13:615–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Artemov D, Mori N, Okollie B, Bhujwalla ZM. MR molecular imaging of the Her-2/neu receptor in breast cancer cells using targeted iron oxide nanoparticles. Magn Reson Med 2003;49:403–8. 51. Moffat BA, Reddy GR, McConville P, Hall DE, Chenevert TL, Kopelman RR, et al. A novel polyacrylamide magnetic nanoparticle contrast agent for molecular imaging using MRI. Mol Imaging 2003;2:324-32.PubMedCrossRefGoogle Scholar
  51. 52.
    Botnar RM, Perez AS, Witte S, Wiethoff AJ, Laredo J, Hamilton J, et al. In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent. Circulation 2004;109:2023–9.PubMedCrossRefGoogle Scholar
  52. 53.
    Fayad ZA. MR imaging for the noninvasive assessment of athero-thrombotic plaques. Magn Reson Imaging Clin N Am 2003;ll:101–13.CrossRefGoogle Scholar
  53. 54.
    Lanza G, Lorenz C, Fischer S, Scott M, Cacheris W, Kaufman R, et al. Enhanced detection of thrombi with a novel fibrin-targeted magnetic resonance imaging agent. Acad Radiol 1998;5(Suppl l):sl73–6.Google Scholar
  54. 55.
    Flacke S, Fischer S, Scott M, Fuhrhop R, Allen J, McLean M, et al. A novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques. Circulation 2001; 104:1280–5.PubMedCrossRefGoogle Scholar
  55. 56.
    Winter P, Caruthers S, Yu X, Song S, Fuhrhop R, Chen J, et al. Improved molecular imaging contrast agent for detection of human thrombus. Mag Reson Med 2003;50:411–6.CrossRefGoogle Scholar
  56. 57.
    Morawski AM, Winter PM, Crowder KC, Caruthers SD, Fuhrhop RW, Scott MJ, et al. Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI. Magn Reson Med 2004;51:480–6.PubMedCrossRefGoogle Scholar
  57. 58.
    Winter PM, Caruthers SD, Kassner A, Harris TD, Chinen LK, Allen JS, et al. Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel alpha(v)beta3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer Res 2003;63:5838–43.PubMedGoogle Scholar
  58. 59.
    Winter PM, Morawski AM, Caruthers SD, Fuhrhop RW, Zhang H, Williams TA, et al. Molecular imaging of angiogenesis in early- stage atherosclerosis with alpha(v)beta3-integrin-targeted nanoparticles. Circulation 2003; 108:2270–4.PubMedCrossRefGoogle Scholar
  59. 60.
    Lanza GM, Yu X, Winter PM, Abendschein DR, Karukstis KK, Scott MJ, et al. Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent: implications for rational therapy of restenosis. Circulation 2002;106:2842–7.PubMedCrossRefGoogle Scholar
  60. 61.
    Fossheim S, Fahlvik A, Klaveness J, Muller R. Paramagnetic liposomes as MRI contrast agents: influence of liposomal physi-cochemical properties on the in vitro relaxivity. Magn Reson Imaging 1999;17:83–9.PubMedCrossRefGoogle Scholar
  61. 62.
    Koenig SH, Ahkong QF, Brown RD III, Lafleur M, Spiller M, Unger E, et al. Permeability of liposomal membranes to water: results from the magnetic field dependence of Tl of solvent protons in suspensions of vesicles with entrapped paramagnetic ions. Magn Reson Med 1992;23:275–86.PubMedCrossRefGoogle Scholar
  62. 63.
    Grant CW, Karlik S, Florio E. A liposomal MRI contrast agent: phosphatidylethanolamine-DTPA. Magn Reson Med 1989;11:236–43.PubMedCrossRefGoogle Scholar
  63. 64.
    Kabalka G, Davis M, Holmberg E, Maruyama K, Huang L. Gadolinium-labeled liposomes containing amphiphilic Gd-DTPA derivatives of varying chain length: targeted MRI contrast enhancement agents for the liver. Magn Reson Imaging 1991; 9:373–7.PubMedCrossRefGoogle Scholar
  64. 65.
    Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KC. Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat Med 1998;4:623–6.PubMedCrossRefGoogle Scholar
  65. 66.
    Hood JD, Cheresh DA. Targeted delivery of mutant Raf kinase to neovessels causes tumor regression. Cold Spring Harb Symp Quant Biol 2002;67:285–91.PubMedCrossRefGoogle Scholar
  66. 67.
    Hood JD, Bednarski M, Frausto R, Guccione S, Reisfeld RA, Xiang R, et al. Tumor regression by targeted gene delivery to the neovasculature. Science 2002;296:2404–7.PubMedCrossRefGoogle Scholar

Copyright information

© American Society of Nuclear Cardiology 2004

Authors and Affiliations

  • Gregory M. Lanza
    • 1
  • Patrick M. Winter
    • 1
  • Shelton D. Caruthers
    • 1
    • 2
  • Anne M. Morawski
    • 1
  • Anne H. Schmieder
    • 1
  • Katherine C. Crowder
    • 1
  • Samuel A. Wickline
    • 1
  1. 1.Division of CardiologyWashington University Medical SchoolSt Louis
  2. 2.Philips Medical Systems, ClevelandOhio

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