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Liquid Perfluorocarbons as Contrast Agents for Ultrasonography and 19F-MRI

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Abstract

Perfluorocarbons (PFCs) are fluorinated compounds that have been used for many years in clinics mainly as gas/oxygen carriers and for liquid ventilation. Besides this main application, PFCs have also been tested as contrast agents for ultrasonography and magnetic resonance imaging since the end of the 1970s. However, most of the PFCs applied as contrast agents for imaging were gaseous. This class of PFCs has been recently substituted by liquid PFCs as ultrasound contrast agents. Additionally, liquid PFCs are being tested as contrast agents for 19F magnetic resonance imaging (MRI), to yield dual contrast agents for both ultrasonography and 19F MRI. This review focuses on the development and applications of the different contrast agents containing liquid perfluorocarbons for ultrasonography and/or MRI: large and small size emulsions (i.e. nanoemulsions) and nanocapsules.

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Abbreviations

FDA:

food and drug administration

GI:

gastrointestinal

i.v.:

intravenous

MR:

magnetic resonance

MRI:

magnetic resonance imaging

MRS:

magnetic resonance spectroscopy

PEG:

polyethylene glycol

PEG-PCL:

PEG-block-poly(caprolactone)

PEG-PLLA:

poly(ethylene glycol)-block-poly(L-lactide)

PFCs:

perfluorocarbons

PFD:

perfluorodecalin

PFH:

perfluorohexane

PFN:

perfluorononane

PFOB:

perfluorooctylbromide

PFP:

perfluoropentane

PLGA:

poly(lactide-co-glycolide)

SNR:

signal-to-noise ratio

THI:

tissue harmonic imaging

UCAs:

ultrasound contrast agents

US:

ultrasound

References

  1. Riess JG. Blood substitutes and other potential biomedical applications of fluorinated colloids. J Fluorine Chem. 2002;114:119–26.

    Article  CAS  Google Scholar 

  2. Gross U, Rudiger S, Reichelt H. Perfluorocarbons—chemically inert but biologically-active. J Fluorine Chem. 1991;53:155–61.

    Article  CAS  Google Scholar 

  3. Lehmler HJ, Bummer PM, Jay M. Liquid ventilation—a new way to deliver drugs to diseased lungs? Chemtech. 1999;29:7–12.

    CAS  Google Scholar 

  4. Liuand MS, Long DM. Perfluoroctylbromide as a diagnostic contrast medium in gastroenterography. Radiology. 1977;122:71–6.

    Google Scholar 

  5. Lowe KC. Perfluorinated blood substitutes and artificial oxygen carriers. Blood Rev. 1999;13:171–84.

    Article  PubMed  CAS  Google Scholar 

  6. Leese PT, Noveck RJ, Shorr JS, Woods CM, Flaim KE, Keipert PE. Randomized safety studies of intravenous perflubron emulsion. I. Effects on coagulation function in healthy volunteers. Anesth Analg. 2000;91:804–11.

    Article  PubMed  CAS  Google Scholar 

  7. Noveck RJ, Shannon EJ, Leese PT, Shorr JS, Flaim KE, Keipert PE, et al. Randomized safety studies of intravenous perflubron emulsion. II. Effects on immune function in healthy volunteers. Anesth Analg. 2000;91:812–22.

    Article  PubMed  CAS  Google Scholar 

  8. Spahn DR. Blood substitutes artificial oxygen carriers: perfluorocarbon emulsions. Crit Care. 1999;3:R93–7.

    Article  PubMed  CAS  Google Scholar 

  9. Lowe KC. Engineering blood: synthetic substitutes from fluorinated compounds. Tissue Eng. 2003;9:389–99.

    Article  PubMed  CAS  Google Scholar 

  10. Gross GW, Greenspan JS, Fox WW, Rubenstein SD, Wolfson MR, Shaffer TH. Use of liquid ventilation with perflubron during extracorporeal membrane-oxygenation—chest radiographic appearances. Radiology. 1995;194:717–20.

    PubMed  CAS  Google Scholar 

  11. Lozano JA, Castro JA, Rodrigo I. Partial liquid ventilation with perfluorocarbons for treatment of ARDS in burns. Burns. 2001;27:635–42.

    Article  PubMed  CAS  Google Scholar 

  12. Hamon I. Liquid ventilation: a new mode of ventilation in neonatology? Arch Pediatr. 1997;4:176–80.

    Article  PubMed  CAS  Google Scholar 

  13. Mattrey RF, Long DM, Multer F, Mitten R, Higgins CB. Perfluoroctylbromide: a reticuloendothelial-specific and tumor-imaging agent for computed tomography. Radiology. 1982;145:755–8.

    PubMed  CAS  Google Scholar 

  14. Young SW, Enzmann DR, Long DM, Muller HH. Perfluoroctylbromide contrast enhancement of malignant neoplasms: preliminary observations. AJR Am J Roentgenol. 1981;137:141–6.

    PubMed  CAS  Google Scholar 

  15. Klibanov AL. Ultrasound molecular imaging with targeted microbubble contrast agents. J Nucl Cardiol. 2007;14:876–84.

    Article  PubMed  Google Scholar 

  16. Mattrey RF. The potential role of perfluorochemicals (PFCs) in diagnostic imaging. Artif Cells Blood Substit Immobil Biotechnol. 1994;22:295–313.

    Article  PubMed  CAS  Google Scholar 

  17. Schutt EG, Klein DH, Mattrey RM, Riess JG. Injectable microbubbles as contrast agents for diagnostic ultrasound imaging: the key role of perfluorochemicals. Angew Chem Int Edit. 2003;42:3218–35.

    Article  CAS  Google Scholar 

  18. Liu Y, Miyoshi H, Nakamura M. Encapsulated ultrasound microbubbles: therapeutic application in drug/gene delivery. J Control Release. 2006;114:89–99.

    Article  PubMed  CAS  Google Scholar 

  19. Dijkmans PA, Juffermans LJ, Musters RJ, van Wamel A, ten Cate FJ, van Gilst W, et al. Microbubbles and ultrasound: from diagnosis to therapy. Eur J Echocardiogr. 2004;5:245–56.

    Article  PubMed  CAS  Google Scholar 

  20. Lanzaand GM, Wickline SA. Targeted ultrasonic contrast agents for molecular imaging and therapy. Curr Probl Cardiol. 2003;28:625–53.

    Article  Google Scholar 

  21. Hernotand S, Klibanov AL. Microbubbles in ultrasound-triggered drug and gene delivery. Adv Drug Deliv Rev. 2008;60:1153–66.

    Article  CAS  Google Scholar 

  22. Oeffinger BE, Wheatley MA. Development and characterization of a nano-scale contrast agent. Ultrasonics. 2004;42:343–7.

    Article  PubMed  CAS  Google Scholar 

  23. Sontum PC. Physicochemical characteristics of Sonazoid (TM), a new contrast agent for ultrasound imaging. Ultrasound Med Biol. 2008;34:824–33.

    Article  PubMed  Google Scholar 

  24. Goldberg B. Ultrasound contrast agents. London: Dunitz; 2001.

    Google Scholar 

  25. Lindner JR. Microbubbles in medical imaging: current applications and future directions. Nat Rev Drug Discov. 2004;3:527–33.

    Article  PubMed  CAS  Google Scholar 

  26. Calliada F, Campani R, Bottinelli O, Bozzini A, Sommaruga MG. Ultrasound contrast agents: basic principles. Eur J Radiol. 1998;27(Suppl 2):S157–60.

    Article  PubMed  Google Scholar 

  27. Grant EG. Sonographic contrast agents in vascular imaging. Seminars in Ultrasound Ct and Mri. 2001;22:25–41.

    Article  CAS  Google Scholar 

  28. Ngo FC, Hall CS, Marsh JN, Fuhrhop RW, Allen JS, Brown P, et al. Evaluation of liquid perfluorocarbon nanoparticles as a blood pool contrast agent utilizing power Doppler harmonic imaging. 2000 Ieee Ultrasonics Symposium Proceedings. 2000;1 and 2:1931–4.

    Google Scholar 

  29. Wickline SA, Hughes M, Ngo FC, Hall CS, Marsh JN, Brown PA, et al. Blood contrast enhancement with a novel, non-gaseous nanoparticle contrast agent. Acad Radiol. 2002;9:S290–3.

    Article  PubMed  Google Scholar 

  30. Bokor D. Diagnostic efficacy of SonoVue. Am J Cardiol. 2000;86:19G–24.

    Article  PubMed  CAS  Google Scholar 

  31. Kitzman DW, Goldman ME, Gillam LD, Cohen JL, Aurigemma GP, Gottdiener JS. Efficacy and safety of the novel ultrasound contrast agent perflutren (definity) in patients with suboptimal baseline left ventricular echocardiographic images. Am J Cardiol. 2000;86:669–74.

    Article  PubMed  CAS  Google Scholar 

  32. Lindner JR, Song J, Jayaweera AR, Sklenar J, Kaul S. Microvascular rheology of Definity microbubbles after intra-arterial and intravenous administration. J Am Soc Echocardiogr. 2002;15:396–403.

    Article  PubMed  Google Scholar 

  33. Cohen JL, Cheirif J, Segar DS, Gillam LD, Gottdiener JS, Hausnerova E, et al. Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial. J Am Coll Cardiol. 1998;32:746–52.

    Article  PubMed  CAS  Google Scholar 

  34. Correas JM, Bridal L, Lesavre A, Mejean A, Claudon M, Helenon O. Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts. Eur Radiol. 2001;11:1316–28.

    Article  PubMed  CAS  Google Scholar 

  35. Straub JA, Chickering DE, Church CC, Shah B, Hanlon T, Bernstein H. Porous PLGA microparticles: AI-700, an intravenously administered ultrasound contrast agent for use in echocardiography. J Control Release. 2005;108:21–32.

    Article  PubMed  CAS  Google Scholar 

  36. Cui W, Bei J, Wang S, Zhi G, Zhao Y, Zhou X, et al. Preparation and evaluation of poly(L-lactide-co-glycolide) (PLGA) microbubbles as a contrast agent for myocardial contrast echocardiography. J Biomed Mater Res B Appl Biomater. 2005;73:171–8.

    PubMed  Google Scholar 

  37. El-Sherif DM, Wheatley MA. Development of a novel method for synthesis of a polymeric ultrasound contrast agent. J Biomed Mater Res A. 2003;66:347–55.

    Article  PubMed  CAS  Google Scholar 

  38. Quay S. Microbubble-based ultrasound contrast agents: the role of gas selection in microbubble persistence. J Ultrasound Med. 1994;13:S9.

    Google Scholar 

  39. Mattrey RF, Scheible FW, Gosink BB, Leopold GR, Long DM, Higgins CB. Perfluoroctylbromide: a liver/spleen-specific and tumor-imaging ultrasound contrast material. Radiology. 1982;145:759–62.

    PubMed  CAS  Google Scholar 

  40. Ragde H, Kenny GM, Murphy GP, Landin K. Transrectal ultrasound microbubble contrast angiography of the prostate. Prostate. 1997;32:279–83.

    Article  PubMed  CAS  Google Scholar 

  41. Ge S, Giraud GG, Shiota T, Pantely GA, Xu J, Gong Z, et al. Microcirculatory flow dynamics during peripheral intravenous injection of echogentm: microscopic visualization of mesenteric microcirculatory flow with simultaneous transthoracic echo imaging in cats. J Am Coll Cardiol. 1995;25:227A.

    Article  Google Scholar 

  42. Cotter B, Duong A, Raisinghani A, Keramati S, Mahmud E, Kwan OL, et al. Myocardial opacification by low doses EchoGen in patients: assessment of preactivation by closed syringe suction. J Am Coll Cardiol. 1996;27:126.

    Article  Google Scholar 

  43. Nihoyannopoulos P, Rallidis L, Correas J-M, Quay SC. Myocardial enhancement following peripheral intravenous injection of activated QW3600 (EchoGen) in normal human volunteers. J Am Coll Cardiol. 1996;27:378.

    Article  Google Scholar 

  44. Grayburn P. Perflenapent emulsion (EchoGen): a new long-acting phase-shift agent for contrast echocardiography. Clin Cardiol. 1997;20:I12–8.

    Article  PubMed  CAS  Google Scholar 

  45. Kornmann LM, Curfs DMJ, Hermeling E, van der Made I, de Winther MPJ, Reneman RS, et al. Perfluorohexane-loaded macrophages as a novel ultrasound contrast agent: a feasibility study. Mol Imaging Biol. 2008;10:264–70.

    Article  PubMed  Google Scholar 

  46. Saha P, Modarai B, Humphries J, Mattock K, Waltham M, Burnand KG, et al. The monocyte/macrophage as a therapeutic target in atherosclerosis. Curr Opin Pharmacol. 2009;9:109–18.

    Article  PubMed  CAS  Google Scholar 

  47. Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R. Biodegradable long-circulating polymeric nanospheres. Science. 1994;263:1600–3.

    Article  PubMed  CAS  Google Scholar 

  48. Yuan F, Dellian M, Fukumura D, Leunig M, Berk DA, Torchilin VP, et al. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res. 1995;55:3752–6.

    PubMed  CAS  Google Scholar 

  49. Gref R, Luck M, Quellec P, Marchand M, Dellacherie E, Harnisch S, et al. ‘Stealth’ corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B Biointerfaces. 2000;18:301–13.

    Article  PubMed  CAS  Google Scholar 

  50. Pasqualini R, Arap W, McDonald DM. Probing the structural and molecular diversity of tumor vasculature. Trends Mol Med. 2002;8:563–71.

    Article  PubMed  CAS  Google Scholar 

  51. Lanza GM, Wallace KD, Scott MJ, Cacheris WP, Abendschein DR, Christy DH, et al. A novel site-targeted ultrasonic contrast agent with broad biomedical application. Circulation. 1996;94:3334–40.

    PubMed  CAS  Google Scholar 

  52. Lanza GM, Abendschein DR, Hall CS, Scott MJ, Scherrer DE, Houseman A, et al. In vivo molecular imaging of stretch-induced tissue factor in carotid arteries with ligand-targeted nanoparticles. J Am Soc Echocardiogr. 2000;13:608–14.

    Article  PubMed  CAS  Google Scholar 

  53. Winslow RM. Blood substitutes. Adv Drug Deliv Rev. 2000;40:131–42.

    Article  PubMed  CAS  Google Scholar 

  54. Hall CS, Marsh JN, Scott MJ, Gaffney PJ, Wickline SA, Lanza GM. Temperature dependence of ultrasonic enhancement with a site-targeted contrast agent. J Acoust Soc Am. 2001;110:1677–84.

    Article  PubMed  CAS  Google Scholar 

  55. Marsh JN, Hall CS, Wickline SA, Lanza GM. Temperature dependence of acoustic impedance for specific fluorocarbon liquids. J Acoust Soc Am. 2002;112:2858–62.

    Article  PubMed  CAS  Google Scholar 

  56. Marsh JN, Hall CS, Scott MJ, Fuhrhop RW, Gaffney PJ, Wickline SA, et al. Improvements in the ultrasonic contrast of targeted perfluorocarbon nanoparticles using an acoustic transmission line model. IEEE Trans Ultrason Ferroelectr Freq Control. 2002;49:29–38.

    Article  PubMed  Google Scholar 

  57. Marsh JN, Partlow KC, Abendschein DR, Scott MJ, Lanza GM, Wickline SA. Molecular imaging with targeted perfluorocarbon nanoparticles: quantification of the concentration dependence of contrast enhancement for binding to sparse cellular epitopes. Ultrasound Med Biol. 2007;33:950–8.

    Article  PubMed  Google Scholar 

  58. Hughes MS, Marsh JN, Zhang H, Woodson AK, Allen JS, Lacy EK, et al. Characterization of digital waveforms using thermodynamic analogs: Detection of contrast-targeted tissue in vivo. IEEE Trans Ultrason Ferroelectr Freq Control. 2006;53:1609–16.

    Article  PubMed  Google Scholar 

  59. Hughes MS, McCarthy JE, Marsh JN, Arbeit JM, Neumann RG, Fuhrhop RW, et al. Properties of an entropy-based signal receiver with an application to ultrasonic molecular imaging. J Acoust Soc Am. 2007;121:3542–57.

    Article  PubMed  CAS  Google Scholar 

  60. Hughes MS, Marsh JN, Arbeit JM, Neumann RG, Fuhrhop RW, Wallace KD, et al. Application of Renyi entropy for ultrasonic molecular imaging. J Acoust Soc Am. 2009;125:3141–5.

    Article  PubMed  CAS  Google Scholar 

  61. Couture O, Bevan PD, Cherin E, Cheung K, Burns PN, Foster FS. Investigating perfluorohexane particles with high-frequency ultrasound. Ultrasound Med Biol. 2006;32:73–82.

    Article  PubMed  Google Scholar 

  62. Couture O, Bevan PD, Cherin E, Cheung K, Burns PN, Foster FS. A model for reflectivity enhancement due to surface bound submicrometer particles. Ultrasound Med Biol. 2006;32:1247–55.

    Article  PubMed  Google Scholar 

  63. El-Sherif DM, Lathia JD, Le NT, Wheatley MA. Ultrasound degradation of novel polymer contrast agents. J Biomed Mater Res A. 2004;68:71–8.

    Article  PubMed  CAS  Google Scholar 

  64. Pisani E, Tsapis N, Paris J, Nicolas V, Cattel L, Fattal E. Polymeric nano/microcapsules of liquid perfluorocarbons for ultrasonic imaging: physical characterization. Langmuir. 2006;22:4397–402.

    Article  PubMed  CAS  Google Scholar 

  65. Pisani E, Tsapis N, Galaz B, Santin M, Berti R, Taulier N, et al. Perfluorooctyl bromide polymeric capsules as dual contrast agents for ultrasonography and magnetic resonance imaging. Adv Funct Mater. 2008;18:2963–71.

    Article  CAS  Google Scholar 

  66. Pisani E, Fattal E, Paris J, Ringard C, Rosilio V, Tsapis N. Surfactant dependent morphology of polymeric capsules of perfluorooctyl bromide: Influence of polymer adsorption at the dichloromethane-water interface. J Colloid Interface Sci. 2008;326:66–71.

    Article  PubMed  CAS  Google Scholar 

  67. Reed AM, Gilding DK. Biodegradable polymers for use in surgery—poly(glycolic)/poly(Iactic acid) homo and copolymers: 2. In vitro degradation. Polymer. 1981;22:494–8.

    Article  CAS  Google Scholar 

  68. Yamaguchiand K, Anderson JM. Invivo biocompatibility studies of medisorb(R) 65/35 D. L-lactide glycolide copolymer microspheres. J Control Release. 1993;24:81–93.

    Article  Google Scholar 

  69. Owens DE 3rd, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006;307:93–102.

    Article  PubMed  CAS  Google Scholar 

  70. Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov. 2003;2:214–21.

    Article  PubMed  CAS  Google Scholar 

  71. Diaz-Lopez R, Tsapis N, Libong D, Chaminade P, Connan C, Chehimi MM, et al. Phospholipid decoration of microcapsules containing perfluorooctyl bromide used as ultrasound contrast agents. Biomaterials. 2009;30:1462–72.

    Article  PubMed  CAS  Google Scholar 

  72. Fang JY, Hung CF, Hua SC, Hwang TL. Acoustically active perfluorocarbon nanoemulsions as drug delivery carriers for camptothecin: drug release and cytotoxicity against cancer cells. Ultrasonics. 2009;49:39–46.

    Article  PubMed  CAS  Google Scholar 

  73. Rapoport N, Gao Z, Kennedy A. Multifunctional nanoparticles for combining ultrasonic tumor imaging and targeted chemotherapy. J Natl Cancer Inst. 2007;99:1095–106.

    Article  PubMed  CAS  Google Scholar 

  74. Gao Z, Kennedy AM, Christensen DA, Rapoport NY. Drug-loaded nano/microbubbles for combining ultrasonography and targeted chemotherapy. Ultrasonics. 2008;48:260–70.

    Article  PubMed  CAS  Google Scholar 

  75. Maeda H. The enhanced permeability and Retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Advan Enzyme Regul. 2001;41:189–207.

    Article  CAS  Google Scholar 

  76. Uchegbu I. Parenteral drug delivery: 1. Pharm J. 1999;263:309–18.

    Google Scholar 

  77. Waters EA, Wickline SA. Contrast agents for MRI. Basic Res Cardiol. 2008;103:114–21.

    Article  PubMed  CAS  Google Scholar 

  78. McKieand S, Brittenden J. (ii) Basic science: magnetic resonance imaging. Curr Orthop. 2005;19:13–9.

    Article  Google Scholar 

  79. Yan G-P, Robinson L, Hogg P. Magnetic resonance imaging contrast agents: overview and perspectives. Radiography. 2007;13:e5–19.

    Article  Google Scholar 

  80. Hengererand A, Grimm J. Molecular magnetic resonance imaging. Biomed Imaging Intervention J. 2006;2:e8.

    Google Scholar 

  81. Caruthers SD, Neubauer AM, Hockett FD, Lamerichs R, Winter PM, Scott MJ, et al. In vitro demonstration using F-19 magnetic resonance to augment molecular imaging with paramagnetic perfluorocarbon nanoparticles at 1.5 Tesla. Invest Radiol. 2006;41:305–12.

    Article  PubMed  Google Scholar 

  82. Holland GN, Bottomley PA, Hinshaw WS. 19F magnetic resonance imaging. J Magn Reson. 1977;28:133–6.

    CAS  Google Scholar 

  83. Kimura A, Narazaki M, Kanazawa Y, Fujiwara H. 19F Magnetic resonance imaging of perfluorooctanoic acid encapsulated in liposome for biodistribution measurement. Magn Reson Imaging. 2004;22:855–60.

    Article  PubMed  CAS  Google Scholar 

  84. Schwarz R, Schuurmans M, Seelig J, Kunnecke B. 19F-MRI of perfluorononane as a novel contrast modality for gastrointestinal imaging. Magn Reson Med. 1999;41:80–6.

    Article  PubMed  CAS  Google Scholar 

  85. Mason RP, Nunnally RL, Antich PP. Tissue oxygenation: a novel determination using 19F surface coil NMR spectroscopy of sequestered perfluorocarbon emulsion. Magn Reson Med. 1991;18:71–9.

    Article  PubMed  CAS  Google Scholar 

  86. Clark LC Jr, Ackerman JL, Thomas SR, Millard RW, Hoffman RE, Pratt RG, et al. Perfluorinated organic liquids and emulsions as biocompatible NMR imaging agents for 19F and dissolved oxygen. Adv Exp Med Biol. 1984;180:835–45.

    PubMed  CAS  Google Scholar 

  87. Mason RP, Shukla H, Antich PP. Oxygent(Tm)—a novel probe of tissue oxygen-tension. Biomaterials Artificial Cells and Immobilization Biotechnology. 1992;20:929–32.

    CAS  Google Scholar 

  88. Mason RP, Shukla H, Antich PP. In vivo oxygen-tension and temperature—simultaneous determination using f-19 nmr-spectroscopy of perfluorocarbon. Magn Reson Med. 1993;29:296–302.

    Article  PubMed  CAS  Google Scholar 

  89. Shukla HP, Mason RP, Storey C, Jeffrey FMH, Antich PP. The relationship of oxygen-tension and myocardial mechanical function—a F-19 Nmr-study. Circulation. 1992;86:693–3.

    Google Scholar 

  90. Shukla HP, Mason RP, Bansal N, Antich PP. Regional myocardial oxygen tension: F-19 MRI of sequestered perfluorocarbon. Magn Reson Med. 1996;35:827–33.

    Article  PubMed  CAS  Google Scholar 

  91. Shukla HP, Mason RP, Woessner DE, Antich PP. Comparison of 3 commercial perfluorocarbon emulsions as high-field F-19 Nmr probes of oxygen-tension and temperature. J Magn Reson B. 1995;106:131–41.

    Article  CAS  Google Scholar 

  92. Thomas SR, Pratt RG, Millard RW, Samaratunga RC, Shiferaw Y, McGoron AJ, et al. In vivo PO2 imaging in the porcine model with perfluorocarbon F-19 NMR at low field. Magn Reson Imaging. 1996;14:103–14.

    Article  PubMed  CAS  Google Scholar 

  93. Mason RP. Non-invasive physiology: 19F NMR of perfluorocarbons. Artif Cells Blood Substit Immobil Biotechnol. 1994;22:1141–53.

    Article  PubMed  CAS  Google Scholar 

  94. Eidelberg D, Johnson G, Barnes D, Tofts PS, Delpy D, Plummer D, et al. 19F NMR imaging of blood oxygenation in the brain. Magn Reson Med. 1988;6:344–52.

    Article  PubMed  CAS  Google Scholar 

  95. Fishman JE, Joseph PM, Floyd TF, Mukherji B, Sloviter HA. Oxygen-sensitive 19F NMR imaging of the vascular system in vivo. Magn Reson Imaging. 1987;5:279–85.

    Article  PubMed  CAS  Google Scholar 

  96. Morawski AM, Winter PM, Yu X, Fuhrhop RW, Scott MJ, Hockett F, et al. Quantitative “magnetic resonance immunohistochemistry” with ligand-targeted (19)F nanoparticles. Magn Reson Med. 2004;52:1255–62.

    Article  PubMed  CAS  Google Scholar 

  97. Winter P, Athey P, Kiefer G, Gulyas G, Frank K, Fuhrhop R, et al. Improved paramagnetic chelate for molecular imaging with MRI. Proceedings of the Fifth International Conference on Scientific and Clinical Apllications of Magnetic Carriers. J Magn Magn Mater. 2005;293:540–5.

    Article  CAS  Google Scholar 

  98. Neubauer AM, Sim H, Winter PM, Caruthers SD, Williams TA, Robertson JD, et al. Nanoparticle pharmacokinetic profiling in vivo using magnetic resonance imaging. Magn Reson Med. 2008;60:1353–61.

    Article  PubMed  Google Scholar 

  99. Neubauer AM, Caruthers SD, Hockett FD, Cyrus T, Robertson JD, Allen JS, et al. Fluorine cardiovascular magnetic resonance angiography in vivo at 1.5 T with perfluorocarbon nanoparticle contrast agents. J Cardiovasc Magn Reson. 2007;9:565–73.

    Article  PubMed  Google Scholar 

  100. Partlow KC, Chen J, Brant JA, Neubauer AM, Meyerrose TE, Creer MH, et al. 19F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. Faseb J. 2007;21:1647–54.

    Article  PubMed  CAS  Google Scholar 

  101. Ruiz-Cabello J, Walczak P, Kedziorek DA, Chacko VP, Schmieder AH, Wickline SA, et al. In vivo “hot spot” MR imaging of neural stem cells using fluorinated nanoparticles. Magn Reson Med. 2008;60:1506–11.

    Article  PubMed  Google Scholar 

  102. Schmieder AH, Caruthers SD, Zhang H, Williams TA, Robertson JD, Wickline SA, et al. Three-dimensional MR mapping of angiogenesis with alpha5beta1(alpha nu beta3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model. Faseb J. 2008;22:4179–89.

    Article  PubMed  CAS  Google Scholar 

  103. Waters EA, Chen J, Allen JS, Zhang H, Lanza GM, Wickline SA. Detection and quantification of angiogenesis in experimental valve disease with integrin-targeted nanoparticles and 19-fluorine MRI/MRS. J Cardiovasc Magn Reson. 2008;10:43.

    Article  PubMed  Google Scholar 

  104. Ahrens ET, Flores R, Xu HY, Morel PA. In vivo imaging platform for tracking immunotherapeutic cells. Nat Biotechnol. 2005;23:983–7.

    Article  PubMed  CAS  Google Scholar 

  105. Srinivas M, Morel PA, Ernst LA, Laidlaw DH, Ahrens ET. Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model. Magn Reson Med. 2007;58:725–34.

    Article  PubMed  CAS  Google Scholar 

  106. Janjic JM, Srinivas M, Kadayakkara DKK, Ahrens ET. Self-delivering nanoemulsions for dual fluorine-19 MRI and fluorescence detection. J Am Chem Soc. 2008;130:2832–41.

    Article  PubMed  CAS  Google Scholar 

  107. Flogel U, Ding Z, Hardung H, Jander S, Reichmann G, Jacoby C, et al. In vivo monitoring of inflammation after cardiac and cerebral ischemia by fluorine magnetic resonance imaging. Circulation. 2008;118:140–8.

    Article  PubMed  Google Scholar 

  108. Webb AG, Wong M, Kolbeck KJ, Magin R, Suslick KS. Sonochemically produced fluorocarbon microspheres: a new class of magnetic resonance imaging agent. J Magn Reson Imaging. 1996;6:675–83.

    Article  PubMed  CAS  Google Scholar 

  109. Nystrom AM, Bartels JW, Du W, Wooley KL. Perfluorocarbon-loaded shell crosslinked knedel-like nanoparticles: lessons regarding polymer mobility and self-assembly. J Polym Sci A-Polym Chem. 2009;47:1023–37.

    Article  CAS  Google Scholar 

  110. Kaneda MM, Caruthers S, Lanza GM, Wickline SA. Perfluorocarbon nanoemulsions for quantitative molecular imaging and targeted therapeutics. Ann Biomed Eng. 2009.

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Acknowledgments

Authors acknowledge financial support from CONACYT, Agence Nationale de la Recherche (ANR ACUVA NT05-3-42548) and Fondation de l’Avenir. Authors would like to thank S. L. Bridal, M. Santin and O. Lucidarme for fruitful discussions.

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Authors and Affiliations

  1. Univ Paris Sud, UMR CNRS 8612, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France

    Raquel Díaz-López, Nicolas Tsapis & Elias Fattal

  2. CNRS, UMR 8612, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France

    Raquel Díaz-López, Nicolas Tsapis & Elias Fattal

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  1. Raquel Díaz-López
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  3. Elias Fattal
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Díaz-López, R., Tsapis, N. & Fattal, E. Liquid Perfluorocarbons as Contrast Agents for Ultrasonography and 19F-MRI. Pharm Res 27, 1–16 (2010). https://doi.org/10.1007/s11095-009-0001-5

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  • DOI: https://doi.org/10.1007/s11095-009-0001-5

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