Skip to main content

Advertisement

Log in

Nanotechnology for Computed Tomography: A Real Potential Recently Disclosed

  • Expert Review
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

In the last decade, nanomaterials have gained considerable attention and interest in the development of new and efficient molecular probes for medical diagnosis and imaging. Compared to traditional contrast agents used from the 70s, this comes from the new possibilities offered by the increased half-life of nanosystems in blood stream, as well as by the specific accumulation in organ of lesions through passive or active targeting mechanisms. Heavy metal or iodinated-loaded nanoparticles are excellent absorbers of X-rays and can offer excellent improvement in medical diagnosis and X-ray imaging. This review aims to propose an accurate state-of-the-art of the emerging applications of nanotechnology in X-ray imaging. Likewise we will discuss and compare all the solutions proposed, and the impact of their composition, formulation methods, and physicochemical properties on their applications, efficiency, and potential industrial scaling-up.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Badea CT, Drangova M, Holdsworth DW, Johnson GA. In vivo small-animal imaging using micro-ct and digital subtraction angiography. Phys Med Biol. 2008;53:R319–50.

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Burghardt AJ, Link TM, Majumdar S. High-resolution computed tomography for clinical imaging of bone microarchitecture. Clin Orthop Relat Res. 2011;469:2179–93.

    PubMed  Google Scholar 

  3. de Kemp RA, Epstein FH, Catana C, Tsui BMW, Ritman EL. Small-animal molecular imaging methods. J Nucl Med. 2010;51:18–32.

    Google Scholar 

  4. Weber E, Fernandez M, Wapner P, Hoffman W. Comparison of x-ray micro-tomography measurements of densities and porosity principally to values measured by mercury porosimetry for carbon-carbon composites. Carbon. 2010;48:2151–8.

    CAS  Google Scholar 

  5. Zagorchev L, Oses P, Zhuang ZW, Moodie K, Mulligan-Kehoe M, Simons M, et al. Micro computed tomography for vascular exploration. J Angiogenesis Res. 2010;2:7–17.

    Google Scholar 

  6. Schambach SJ, Bag S, Groden C, Schilling L, Brockmann MA. Vascular imaging in small rodents using micro-ct. Methods. 2010;50:26–35.

    CAS  PubMed  Google Scholar 

  7. Ritman EL. Small-animal ct: Its difference from, and impact on, clinical ct. Nucl Instrum Methods Phys Res A. 2007;580:968–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Tsui BMW, Kraitchman DL. Recent advances in small-animal cardiovascular imaging. J Nucl Med. 2009;50:667–70.

    PubMed Central  PubMed  Google Scholar 

  9. Li J, Chaudhary A, Chmura SJ, Pelizzari C, Rajh T, Wietholt C, et al. A novel functional ct contrast agent for molecular imaging of cancer. Phys Med Biol. 2010;55:4389–97.

    PubMed  Google Scholar 

  10. Graham KC, Wirtzfeld LA, MacKenzie LT, Postenka CO, Groom AC, MacDonald IC, et al. Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models. Cancer Res. 2005;65:5231–7.

    CAS  PubMed  Google Scholar 

  11. van Tellingen O, Beijnen J, Verweij J, Scherrenburg E, Nooijen W, Sparreboom A. Rapid esterase-sensitive breakdown of polysorbate 80 and its impact on the plasma pharmacokinetics of docetaxel and metabolites in mice. Clin Cancer Res. 1999;5:2918–24.

    PubMed  Google Scholar 

  12. Storm G, Belliot SO, Daemen T, Lasic DD. Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system. Adv Drug Deliv Rev. 1995;17:31–48.

    CAS  Google Scholar 

  13. Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev. 2002;54:631–51.

    CAS  PubMed  Google Scholar 

  14. Haley B, Frenkel E. Nanoparticles for drug delivery in cancer treatment. Urol Oncol. 2008;26:57–64.

    CAS  PubMed  Google Scholar 

  15. Singh R, Lillard Jr JW. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009;86:215–23.

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Torchilin VP, Trubetskoy VS. Which polymers can make nanoparticulate drug carriers long-circulating? Adv Drug Deliv Rev. 1995;16:141–55.

    CAS  Google Scholar 

  17. Ghaghada KB, Badea CT, Karumbaiah L, Fettig N, Bellamkonda RV, Johnson GA, et al. Evaluation of tumor microenvironment in an animal model using a nanoparticle contrast agent in computed tomography imaging. Acad Radiol. 2011;18:20–30.

    PubMed Central  PubMed  Google Scholar 

  18. Kao CY, Hoffman EA, Beck KC, Bellamkonda RV, Annapragada AV. Long-residence-time nano-scale liposomal iohexol for x-ray-based blood pool imaging. Acad Radiol. 2003;10:475–83.

    PubMed  Google Scholar 

  19. Martiniova L, Schimel D, Lai EW, Limpuangthip A, Kvetnansky R, Pacak K. In vivo micro-ct imaging of liver lesions in small animal models. Methods. 2010;50:20–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Rabin O, Manuel Perez J, Grimm J, Wojtkiewicz G, Weissleder R. An x-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater. 2006;5:118–22.

    CAS  PubMed  Google Scholar 

  21. Torchilin VP, Frank-Kamenetsky MD, Wolf GL. Ct visualization of blood pool in rats by using long-circulating, iodine-containing micelles. Acad Radiol. 1999;6:61–5.

    CAS  PubMed  Google Scholar 

  22. Almajdub M, Nejjari M, Poncet G, Magnier L, Chereul E, Roche C, et al. In-vivo high-resolution x-ray microtomography for liver and spleen tumor assessment in mice. Contrast Media Mol Imaging. 2007;2:88–93.

    CAS  PubMed  Google Scholar 

  23. Kim HW, Cai QY, Jun HY, Chon KS, Park SH, Byun SJ, et al. Micro-ct imaging with a hepatocyte-selective contrast agent for detecting liver metastasis in living mice. Acad Radiol. 2008;15:1282–90.

    PubMed  Google Scholar 

  24. Ohta S, Lai EW, Morris JC, Bakan DA, Klaunberg B, Cleary S, et al. Microct for high-resolution imaging of ectopic pheochromocytoma tumors in the liver of nude mice. Int J Cancer. 2006;119:2236–41.

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Havron A, Seltzer S, Davis MA, Shulkin P. Radiopaque liposomes: A promising new contrast material for computed tomography of the spleen. Radiology. 1981;140:507–11.

    CAS  PubMed  Google Scholar 

  26. Ryan PJ, Davis MA, DeGaeta LR, Woda B, Meichior DL. Liposomes loaded with contrast material for image enhancement in computed tomograpy. Radiology. 1984;152:759–62.

    CAS  PubMed  Google Scholar 

  27. Benita S, Poly P, Puisieux F, Delattre J. Radiopaque liposomes: effect of formulation conditions on encapsulation efficiency. J Pharm Sci. 1984;73(12):1751–5.

    CAS  PubMed  Google Scholar 

  28. Seltzer SE, Blau M, Herman LW, Hooshmand RL, Herman LA, Adams DF, et al. Contrast material-carrying liposomes: Blodistributlon, clearance, and imaging characteristics. Radiology. 1995;194:775–81.

    CAS  PubMed  Google Scholar 

  29. Zingel C, Sachse A, Ršssling GL, MŸller RH. Lyophilization and rehydration of iopromide-carrying liposomes. Int J Pharm. 1996;140:13–24.

    CAS  Google Scholar 

  30. Desser TS, Rubin DL, Muller H, McIntire GL, Bacon ER, Toner JL. Blood pool and liver enhancement in ct with liposomal iodixanol: Comparison with iohexol. Acad Radiol. 1999;6:176–83.

    CAS  PubMed  Google Scholar 

  31. Schmiedl UP, Krause W, Leike J, Sachse A. Ct blood pool enhancement in primates with lopromide-carrying liposomes containing soy phosphatidyl glycerol. Acad Radiol. 1999;6:164–9.

    CAS  PubMed  Google Scholar 

  32. Harrington KJ, Mohammadtaghi S, Uster PS, Glass D, Peters AM, Vile RG, et al. Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res. 2001;7:243–54.

    CAS  PubMed  Google Scholar 

  33. Leike JL, Sachse A, Rupp K. Characterization of continuously extruded iopromide-carrying liposomes for computed tomography blood-pool imaging. Investig radiol. 2001;36(6):303–8.

    CAS  Google Scholar 

  34. Leander P, Höglund P, Borseth A, Kloster Y, Berg A. A new liposomal liver-specific contrast agent for ct: first human phase-i clinical trial assessing efficacy and safety. Eur Radiol. 2001;11:698–704.

    CAS  PubMed  Google Scholar 

  35. Mukundan Jr S, Ghaghada KB, Badea CT, Kao CY, Hedlund LW, Provenzale JM, et al. A liposomal nanoscale contrast agent for preclinical ct in mice. Am J Roentgenol. 2006;186:300–7.

    Google Scholar 

  36. Montet X, Pastor C, VallŽe JP, Becker C, Geissbuhler A, Morel D, et al. Improved visualization of vessels and hepatic tumors by micro-computed tomography (ct) using iodinated liposomes. Investig Radiol. 2007;42(9):652–8.

    CAS  Google Scholar 

  37. Burke SJ, Annapragada A, Hoffman EA, Chen E, Ghaghada KB, Sieren J, et al. Imaging of pulmonary embolism and t-pa therapy effects using mdct and liposomal iohexol blood pool agent. preliminary results in a rabbit model. Acad Radiol. 2007;14:355–62.

    PubMed Central  PubMed  Google Scholar 

  38. Zheng J, Liu J, Dunne M, Jaffray DA, Allen C. In vivo performance of a liposomal vascular contrast agent for ct and mr-based image guidance applications. Pharm Res. 2007;24(6):1193–201.

    CAS  PubMed  Google Scholar 

  39. Badea C, Samei E, Ghaghada K, Saunders R, Yuan H, Qi Y, et al. Utility of a prototype liposomal contrast agent for x-ray imaging of breast cancer: a proof of concept using micro-ct in small animals. Proc Soc Photo Opt Instrum Eng. 2008;9:691303.1–691303.9.

    Google Scholar 

  40. Elrod DB, Partha R, Danila D, Casscells SW, Conyers JL. An iodinated liposomal computed tomographic contrast agent prepared from a diiodophosphatidylcholine lipid. Nanomed-Nanotechnol Biol Med. 2009;5:42–5.

    CAS  Google Scholar 

  41. Weichert JP, Longino MA, Bakan DA, Spigarelli MG, Chou T, Schwendner SW, et al. Polyiodinated triglyceride analogs as potential computed tomography imaging agents for the liver. J Med Chem. 1995;38:636–46.

    CAS  PubMed  Google Scholar 

  42. Bakan DA, Longino MA, Weichert JP, Counsell RE. Physicochemical characterization of a synthetic lipid emulsion for hepatocyte-selective delivery of lipophilic compounds: Application to polyiodinated triglycerides as contrast agents for computed tomography. J Pharm Sci. 1996;85:908–14.

    CAS  PubMed  Google Scholar 

  43. Lee Jr F, Chosy S, Naidu S, Goldfarb S, Weichert J, Bakan D, et al. Ct depiction of experimental liver tumors: Contrast enhancement with hepatocyte-selective iodinated triglyceride versus conventional techniques. Radiology. 1997;203(2):465–70.

    PubMed  Google Scholar 

  44. Weichert J, Lee Jr F, Longino M, Chosy S, Counsell R. Lipid-based blood-pool ct imaging of the liver. Acad radiol. 1998;5:16–9.

    Google Scholar 

  45. Weichert JP, Lee FT, Chosy SG, Longino MA, Kuhlman JE, Heisey DM, et al. Combined hepatocyte-selective and blood-pool contrast agents for the ct detection of experimental liver tumors in rabbits. Radiology. 2000;216:865–71.

    CAS  PubMed  Google Scholar 

  46. Weber SM, Peterson KA, Durkee B, Qi C, Longino M, Warner T, et al. Imaging of murine liver tumor using microct with a hepatocyte-selective contrast agent: accuracy is dependent on adequate contrast enhancement. J Surg Res. 2004;119:41–5.

    CAS  PubMed  Google Scholar 

  47. Badea C, Fubara B, Hedlund L, Johnson G. 4-d micro-ct of the mouse heart. Mol Imaging. 2005;4(2):110–6.

    PubMed  Google Scholar 

  48. Ford N, Graham K, Groom A, MacDonald I, Chambers A, Holdsworth D. Time-course characterization of the computed tomography contrast enhancement of an iodinated blood-pool contrast agent in mice using a volumetric flat-panel equipped computed tomography scanner. Investig Radiol. 2006;41(4):384–90.

    Google Scholar 

  49. Henning T, Weber AW, Bauer JS, Meier R, Carlsen JM, Sutton EJ, et al. Imaging characteristics of dhog, a hepatobiliary contrast agent for preclinical microct in mice. Acad Radiol. 2008;15:342–9.

    PubMed  Google Scholar 

  50. Willekens I, Lahoutte T, Buls N, Vanhove C, Deklerck R, Bossuyt A, et al. Time-course of contrast enhancement in spleen and liver with exia 160, fenestra lc, and vc. Mol Imaging Biol. 2009;11:128–35.

    PubMed  Google Scholar 

  51. Trubetskoy VS, Gazelle GS, Wolf GL, Torchilin VP. Block-copolymer of polyethylene glycol and polylysine as a carrier of organic iodine: design of long-circulating particulate contrast medium for x-ray computed tomography. J Drug Target. 1997;4:381–8.

    CAS  PubMed  Google Scholar 

  52. Torchilin VP. Polymeric micelles in diagnostic imaging. Colloid Surf B-Biointerfaces. 1999;16:305–19.

    CAS  Google Scholar 

  53. Trubetskoy V. Polymeric micelles as carriers of diagnostic agents. Adv Drug Deliv Rev. 1999;37(1–3):81–8.

    CAS  PubMed  Google Scholar 

  54. Torchilin V. Polymeric contrast agents for medical imaging. Curr Pharm Biotechnol. 2000;1(2):183–215.

    CAS  PubMed  Google Scholar 

  55. Yordanov A, Mollov N, Lodder A, Woller E, Cloninger M, Walbridge S, et al. A water-soluble triiodo amino acid and its dendrimer conjugate for computerized tomography (ct) imaging. J Serb Chem Soc. 2005;70:163–70.

    CAS  Google Scholar 

  56. Yezhelyev MV, Gao X, Xing Y, Al-Hajj A, Nie S, OÕRegan RM. Emerging use of nanoparticles in diagnosis and treatment of breast cancer. Lancet Oncol. 2006;7:657–67.

    CAS  PubMed  Google Scholar 

  57. Fu Y, Nitecki DE, Maltby D, Simon GH, Berejnoi K, Raatschen HJ, et al. Dendritic iodinated contrast agents with peg-cores for ct imaging: synthesis and preliminary characterization. Bioconjugate Chem. 2006;17:1043–56.

    CAS  Google Scholar 

  58. Ho Kong, W., Jae Lee, W., Yun Cui, Z., Hyun Bae, K., Gwan Park, T., Hoon Kim, J., Park, K., Won Seo, S.: Nanoparticulate carrier containing water-insoluble iodinated oil as a multifunctional contrast agent for computed tomography imaging. Biomaterials 28, 5555Ð5561 (2007)

  59. Galperin A, Margel D, Baniel J, Dank G, Biton H, Margel S. Radiopaque iodinated polymeric nanoparticles for x-ray imaging applications. Biomaterials. 2007;28:4461–8.

    CAS  PubMed  Google Scholar 

  60. Jakhmola A, Anton N, Vandamme T. Inorganic nanoparticles based contrast agents for x-ray computed tomography. Adv Healthcare Mater. 2012;1:413–31.

    CAS  Google Scholar 

  61. Storm G, Crommelin DA. Liposomes: quo vadis? PSTT. 1998;1:19–31.

    CAS  Google Scholar 

  62. Karathanasis E, Chan L, Balusu SR, DÕOrsi CJ, Annapragada AV, Sechopoulos I, et al. Multifunctional nanocarriers for mammographic quantification of tumor dosing and prognosis of breast cancer therapy. Biomaterials. 2008;29:4815–22.

    CAS  PubMed  Google Scholar 

  63. Zheng J, Hoisak J, Allen C, Jaffray D. Longitudinal vascular imaging using a novel nano-encapsulated ct and mr contrast agent. Proc Soc Photo Opt Instrum Eng. 2007;6511(2):65,111–2.

    Google Scholar 

  64. Perkins G, Zheng J, Brock K, Allen C, Jaffray D. Nanoengineered multimodal contrast agent for medical imaging guidance. Proc Soc Photo Opt Instrum Eng. 2005;5746(1):31–9.

    Google Scholar 

  65. Allen T, Hansen C. Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim Biophys Acta. 1991;1068:122–41.

    Google Scholar 

  66. Klibanov A, Maruyama K, Bekerleg A, Torchilin V, Huang L. Activity of amphipathic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target. Biochim Biophys Acta. 1991;1062:142–8.

    CAS  PubMed  Google Scholar 

  67. Maruyama K, Yuda T, Okamoto A, Kojima S, Suginaka A, Iwatsuru M. Prolonged circulation time in vivo of large unilamellar liposomes composed of distearoyl phosphatdylcholine and cholesterol containing amphipathic poly(ethylene glycol). Biochim Biophys Acta. 1992;1128:44–9.

    CAS  PubMed  Google Scholar 

  68. Torchilin V, Papisov M. Why do polyethylene glycol-coated liposomes circulate so long? J Liposome Res. 1994;4:725–39.

    Google Scholar 

  69. Phillips W, Klipper R, Awasthi V, Rudolph A, Cliff R, Kwasiborski V, et al. Polyethylene glycol modified liposome encapsulated hemoglobin: a long circulating red cell substitute. J Pharmacol Exp Ther. 1999;288:665–70.

    CAS  PubMed  Google Scholar 

  70. Olson F, Hunt C, Szoka F, Vail W, Papahadjopoulos D. Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes. Biochim Biophys Acta. 1979;557:9–23.

    CAS  PubMed  Google Scholar 

  71. Szoka F, Olson F, Heath T, Vail W, Mayhew E, Papahadjopoulos D. Preparation of unilamellar liposomes of intermediate size (0.1–0.2 mm) by a combination of reverse phase evaporation and extrusion through polycarbonate membranes. Biochim. Biophys. Acta. 1980;601:559–71.

    CAS  Google Scholar 

  72. Zheng J, Perkins G, Kirilova A, Allen C, Jaffray D. Multimodal contrast agent for combined computed tomography and magnetic resonance imaging applications. Invest Radiol. 2006;41(3):339–48.

    PubMed  Google Scholar 

  73. Bourin M, Jolliet P, Ballereau F. An overview of the clinical pharmacokinetics of x-ray contrast media. Clin Pharmacokinet. 1997;32(3):180–93.

    CAS  PubMed  Google Scholar 

  74. Drummond D, Meyer O, Hong K, Kirpotin D, Papahadjopoulous D. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev. 1999;51(4):691–742.

    CAS  PubMed  Google Scholar 

  75. Schneider T, Sachse A, Rossling G, Brandl M. Generation of contrast-carrying liposomes of defined size with a new continuous high pressure extrusion method. Int J Pharm. 1995;117:1–12.

    CAS  Google Scholar 

  76. Abra R, Hunt C. Liposome disposition in vivo. iii. dose and vesicle-size effects. Biochim Biophys Acta. 1981;666:493–503.

    CAS  PubMed  Google Scholar 

  77. Hwang, K.: Liposome Pharmacokinetics, in Liposomes: From Biophysics to Therapeutics. Marcel Dekker (1987)

  78. Senior J, Crawley J, Gregoriadis G. Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection. Biochim Biophys Acta. 1985;839:1–8.

    CAS  PubMed  Google Scholar 

  79. Gregoriadis G, Senior J. The phospholipid component of small unilamellar liposomes controls the rate of clearance of entrapped solutes from the circulation. FEBS Lett. 1980;119:43–6.

    CAS  PubMed  Google Scholar 

  80. Jacobsen PB. Larsen, Konarboland, R., Skotland, T.: Biotransformation of nonionic x-ray contrast agents in vivo and in vitro. Drug Metab Dispos. 1999;27(10):1205–13.

    CAS  PubMed  Google Scholar 

  81. Allen T, Murray L, MacKeigan S, Shah M. Chronic liposome administration in mice: Effects on reticuloendothelial function and tissue distribution. J Pharmacol Exp Ther. 1984;229:267–75.

    CAS  PubMed  Google Scholar 

  82. Allen T, Smuckler E. Liver pathology accompanying chronic liposome administration in mouse. Res Commun Chem Pathol Pharmacol. 1985;50:281–90.

    CAS  PubMed  Google Scholar 

  83. Allen T, Murray L, Alving C, Moe J. Effects of the murine mononuclear phagocyte system of chronic administration of liposomes containing cytotoxic drug or lipid a compared with empty liposomes. Can J Physiol Pharmacol. 1987;65:185–90.

    CAS  PubMed  Google Scholar 

  84. Storm G, Oussoren C, Peeters P, Barenholz Y. Tolerability of liposomes in vivo, in Liposome Technology. FL: Boca Raton; 1993.

    Google Scholar 

  85. Mutzel W, Speck U. Tolerance and biochemical pharmacology of iopromide. Fortschr Gebiete Rontgenstrahlen Nuklearmedizin. 1983;118:11–7.

    CAS  Google Scholar 

  86. Kweon S, Lee HJ, Hyung WJ, Suh J, Lim JS, Lim SJ. Liposomes coloaded with iopamidol/lipiodol as a res-targeted contrast agent for computed tomography imaging. Pharm Res. 2010;27:1408–15.

    CAS  PubMed  Google Scholar 

  87. Zheng J, Jaffray D, Allen C. Quantitative ct imaging of the spatial and temporal distribution of liposomes in a rabbit tumor model. Mol Pharm. 2009;6:571–80.

    CAS  PubMed  Google Scholar 

  88. Karathanasis E, Suryanarayanan S, Balusu SR, McNeeley K, Sechopoulos I, Karellas A, et al. Imaging nanoprobe for prediction of outcome of nanoparticle chemotherapy by using mammography. Radiology. 2009;250:398–406.

    PubMed  Google Scholar 

  89. Samei E, Saunders RS, Badea CT, Ghaghada KB, Hedlund LW, Qi Y, et al. Micro-ct imaging of breast tumors in rodents using a liposomal, nanoparticle contrast agents. Int J Nanomed. 2009;4:277–82.

    CAS  Google Scholar 

  90. Wyss C, Schaefer SC, Juillerat-Jeanneret L, Lagopoulos L, Lehr HA, Becker CD, et al. Molecular imaging by micro-ct: specific e-selectin imaging. Eur Radiol. 2009;19:2487–94.

    PubMed  Google Scholar 

  91. Austrup F, Vestweber D, Borges E, Lohning M, Brauer R, Herz U, et al. P- and e-selectin mediate recruitment of t-helper-1 but not t-helper-2 cells into inflamed tissues. Nature. 1997;385:81–3.

    CAS  PubMed  Google Scholar 

  92. Graves BJ, Crowther RL, Chandran C, Rumberger JM, Li S, Huang KS, et al. Insight into e-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/egf domains. Nature. 1994;367:532–8.

    CAS  PubMed  Google Scholar 

  93. Anton N, Benoit JP, Saulnier P. Design and production of nanoparticles formulated from nano-emulsion templates – a review. J Control Release. 2008;128:185–99.

    CAS  PubMed  Google Scholar 

  94. Anton N, Vandamme TF. The universality of low-energy nano-emulsification. Int J Pharm. 2009;377:142–7.

    CAS  PubMed  Google Scholar 

  95. Anton N, Mojzisova H, Porcher E, Benoit JP, Saulnier P. Reverse micelle-loaded lipid nano-emulsions: New technology for nano-encapsulation of hydrophilic materials. Int J Pharm. 2010;398:204–9.

    CAS  PubMed  Google Scholar 

  96. Anton N, Vandamme T. Nano-emulsions and micro-emulsions: Clarifications of the critical differences. Pharm Res. 2011;28:978–95.

    CAS  PubMed  Google Scholar 

  97. Fryd M, Mason T. Advanced nanoemulsions Annu Rev Phys Chem. 2012;63:493–518.

    CAS  Google Scholar 

  98. McClements D. Nanoemulsions versus microemulsions: Terminology, differences, and similarities. Soft Matter. 2012;8:1719–29.

    CAS  Google Scholar 

  99. Hallouard F, Anton N, Choquet P, Constantinesco A, Vandamme T. Iodinated blood pool contrast media for preclinical x-ray imaging applications. Biomaterials. 2010;31:6249–68.

    CAS  PubMed  Google Scholar 

  100. Hallouard F, Anton N, Zuber G, Choquet P, Li X, Arntz Y, et al. Radiopaque iodinated nano-emulsions for preclinical x-ray imaging. RSC Advances. 2011;1:792–801.

    CAS  Google Scholar 

  101. Hallouard, F., Briançon, S., Anton, N., Li, X., Vandamme, T., Fessi, H.: Iodinated nano-emulsions as contrast agents for preclinical x-ray imaging, impact of the free surfactants on the pharmacokinetics. Eur. J. Pharm. Biopharm. 2013;83:54–62.

    Google Scholar 

  102. Li X, Anton N, Zuber G, Zhao M, Hallouard F, Fessi H, et al. Iodinated α-tocopherol nano-emulsions as non-toxic contrast agents for preclinical x-ray imaging. Biomaterials. 2013;34:481–91.

    CAS  PubMed  Google Scholar 

  103. Badea CT, Hedlund LW, de Lin M, Boslego Mackel JF, Johnson GA. Tumor imaging in small animals with a combined micro-ct/micro-dsa system using iodinated conventional and blood pool contrast agents. Contrast Media Mol Imaging. 2006;1:153–64.

    CAS  PubMed  Google Scholar 

  104. Weichert JP, Groziak MP, Longino MA, Schwendner SW, Counsell RE. Potential tumor- or organ-imaging agents. 27. polyiodinated 1,3-disubstituted and 1,2,3-trisubstituted triacylglycerols. J Med Chem. 1986;29:2457–65.

    CAS  PubMed  Google Scholar 

  105. Weichert JP, Longino MA, Schwendner SW, Counsell RE. Potential tumor- or organ-imaging agents. 26. polyiodinated 2-substituted triacylglycerols as hepatographic agents. J Med Chem. 1986;29:1674–82.

    CAS  PubMed  Google Scholar 

  106. de Vries A, Custers E, Lub J, van den Bosch S, Nicolay K, Grüll H. Block-copolymer-stabilized iodinated emulsions for use as ct contrast agents. Biomaterials. 2010;31:6537–44.

    PubMed  Google Scholar 

  107. Aprahamian M, Bour G, Akladios CY, Fylaktakidou K, Greferath R, Soler L, et al. Myo-inositoltrispyrophosphate treatment leads to hif-1α suppression and eradication of early hepatoma tumors in rats. ChemBioChem. 2011;12:777–83.

    CAS  PubMed  Google Scholar 

  108. Guo R, Wang H, Peng C, Shen M, Pan M, Cao X, et al. X-ray attenuation property of dendrimer-entrapped gold nanoparticles. J Phys Chem C. 2009;114:50–6.

    Google Scholar 

  109. Kojima C, Umeda Y, Ogawa M, Harada A, Magata Y, Kono K. X-ray computed tomography contrast agents prepared by seeded growth of gold nanoparticles in pegylated dendrimer. Nanotechnology. 2010;21:245,104.

    Google Scholar 

  110. Peng C, Wang H, Guo R, Shen M, Cao X, Zhu M, et al. Acetylation of dendrimer-entrapped gold nanoparticles: Synthesis, stability, and x-ray attenuation properties. J Appl Polym Sci. 2011;119:1673–82.

    CAS  Google Scholar 

  111. Peng C, Zheng L, Chen Q, Shen M, Guo R, Wang H, et al. Pegylated dendrimer-entrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography. Biomaterials. 2012;33:1107–19.

    CAS  PubMed  Google Scholar 

  112. Boote E, Fent G, Kattumuri V, Casteel S, Katti K, Chanda N, et al. Gold nanoparticle contrast in a phantom and juvenile swine: models for molecular imaging of human organs using x-ray computed tomography. Acad Radiol. 2010;17:410–7.

    PubMed Central  PubMed  Google Scholar 

  113. Kattumuri V, Katti K, Bhaskaran S, Boote EJ, Casteel SW, Fent GM, et al. Gum arabic as a phytochemical construct for the stabilization of gold nanoparticles: in vivo pharmacokinetics and x-ray-contrast-imaging studies. Small. 2007;3:333–41.

    CAS  PubMed  Google Scholar 

  114. de Krafft KE, Xie Z, Cao G, Tran S, Ma L, Zhou OZ, et al. Iodinated nanoscale coordination polymers as potential contrast agents for computed tomography. Angew Chem-Int Edit. 2009;48:9901–4.

    Google Scholar 

  115. Bosman AW, Janssen HM, Meijer EW. About dendrimers: structure, physical properties, and applications. Chem Rev. 1999;99:1665–88.

    CAS  PubMed  Google Scholar 

  116. Koo OM, Rubinstein I, Onyuksel H. Role of nanotechnology in targeted drug delivery and imaging: a concise review. Nanomed-Nanotechnol Biol Med. 2005;1:193–212.

    CAS  Google Scholar 

  117. Guo R, Wang H, Peng C, Shen M, Zheng L, Zhang G, et al. Enhanced x-ray attenuation property of dendrimer-entrapped gold nanoparticles complexed with diatrizoic acid. J Mater Chem. 2011;21:5120–7.

    CAS  Google Scholar 

  118. Roberts J, Bhalgat M, Zera R. Preliminary biological evaluation of polyamidoamine (pamam) starburstª dendrimers. J Biomed Mater Res. 1996;30(1):53–65.

    CAS  PubMed  Google Scholar 

  119. Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, Weener J, et al. Dendrimers: Relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of i-labelled polyamidoamine dendrimers in vivo. J Control Release. 2000;65(1–2):133–48.

    CAS  PubMed  Google Scholar 

  120. Zinselmeyer B, Mackay S, Schatzlein A, Uchegbu I. The lower-generation polypropylenimine dendrimers are effective gene-transfer agents. Pharm Res. 2002;19(7):960–7.

    CAS  PubMed  Google Scholar 

  121. Gajbhiye V, Vijayaraj Kumar P, Tekade R, Jain N. Pegylated ppi dendritic architectures for sustained delivery of h2 receptor antagonist. Eur J Med Chem. 2009;44(3):1155–66.

    CAS  PubMed  Google Scholar 

  122. Torchilin VP. Structure and design of polymeric surfactant-based drug delivery systems. J Control Release. 2001;73:137–72.

    CAS  PubMed  Google Scholar 

  123. Lukyanov AN, Torchilin VP. Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs. Adv Drug Deliv Rev. 2004;56:1273–89.

    CAS  PubMed  Google Scholar 

  124. Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD. Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small. 2005;1:325–7.

    CAS  PubMed  Google Scholar 

  125. Dalsin JL, Hu BH, Lee BP, Messersmith PB. Mussel adhesive protein mimetic polymers for the preparation of nonfouling surfaces. J Am Chem Soc. 2003;125:4253–8.

    CAS  PubMed  Google Scholar 

  126. Hainfeld JF, Slatkin DN, Focella TM, Smilowitz HM. Gold nanoparticles: a new x-ray contrast agents. Br J Radiol. 2006;79:248–53.

    CAS  PubMed  Google Scholar 

  127. Hiebert L. The uptake of heparin by liver sinusoidal cells in normal and atherosclerotic rabbits. Thromb Res. 1981;21:383–90.

    CAS  PubMed  Google Scholar 

  128. Kim D, Park S, Lee JH, Jeong YY, Jon S. Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo x-ray computed tomography imaging. J Am Chem Soc. 2007;129:7661–5.

    CAS  PubMed  Google Scholar 

  129. Park K, Kim K, Kwon IC, Kim SK, Lee S, Lee DY, et al. Preparation and characterization of self-assembled nanoparticles of heparin-deoxycholic acid conjugates. Langmuir. 2004;20:11726–11731.

    Google Scholar 

  130. Shukla R, Bansal V, Chaudhary M, Basu A, Bhonde RR, Sastry M. Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview. Langmuir. 2005;21:10644–10654.

    Google Scholar 

  131. Cai QY, Kim SH, Choi KS, Kim SY, Byun SJ, Kim KW, et al. Colloidal gold nanoparticles as a blood-pool contrast agent for x-ray computed tomography in mice. Invest Radiol. 2007;42:797–806.

    CAS  PubMed  Google Scholar 

  132. Sun I, Eun D, Na JH, Lee S, Kim I, Youn I, et al. Heparin-coated gold nanoparticles for liver-specific ct imaging. Chem-Eur J. 2009;15:13341–13347.

    Google Scholar 

  133. Eck W, Nicholson AI, Zentgraf H, Semmler W, Bartling S. Anti-cd4-targeted gold nanoparticles induce specific contrast enhancement of peripheral lymph nodes in x-ray computed tomography of live mice. Nano Lett. 2010;10:2318–22.

    CAS  PubMed  Google Scholar 

  134. Chanda N, Kattumuri V, Shukla R, Zambre A, Katti K, Upendran A, et al. Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity. Proc Natl Acad Sci USA. 2010;107:8760–5.

    CAS  PubMed  Google Scholar 

  135. Zhang Z, Ross RD, Roeder RK. Preparation of functionalized gold nanoparticles as a targeted x-ray contrast agent for damaged bone tissue. Nanoscale. 2010;2:582–6.

    CAS  PubMed  Google Scholar 

  136. Hainfeld JF, O’Connor MJ, Dilmanian FA, Slatkin DN, Adams DJ, Smilowitz HM. Micro-ct enables microlocalisation and quantification of her2-targeted gold nanoparticles within tumour regions. Br J Radiol. 2011;84:526–33.

    CAS  PubMed  Google Scholar 

  137. Boll H, Nittka S, Doyon F, Neumaier M, Marx A, Kramer M, et al. Micro-ct based experimental liver imaging using a nanoparticulate contrast agent: A longitudinal study in mice. PLoS ONE. 2011;6(e25):1–6.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nicolas Anton.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anton, N., Vandamme, T.F. Nanotechnology for Computed Tomography: A Real Potential Recently Disclosed. Pharm Res 31, 20–34 (2014). https://doi.org/10.1007/s11095-013-1131-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-013-1131-3

KEY WORDS

Navigation