Use of Radiolabeled Liposomes for Tumor Imaging

  • Tamer Elbayoumi
  • Vladimir Torchilin
Part of the Fundamental Biomedical Technologies book series (FBMT, volume 102)


Liposomes or microscopic phospholipid vesicles have a long history of medical applications as drug carriers. Among other pharmaceutical agents, liposomes have been used as carrier systems for various imaging agents including those used in gamma-scintigraphy. This chapter provides a brief description of the preparation and application of radiolabeled liposomes. Various methods of liposome labeling with gamma-emitting isotopes are considered as well as specific problems associated with obtaining the optimal preparations and results of both animal experiments with radiolabeled liposomes and early clinical data. The examples of using the radiolabeled liposomes for the development of the liposomal anti-cancer drugs are also presented.


Imaging Agent Liposomal Doxorubicin Lewis Lung Carcinoma Scintigraphic Imaging Diethylene Triamine Pentaacetic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abra, R.M., Hunt, C.A.,1982. Liposome disposition in vivo IV: the interaction of sequential doses of liposomes having different diameters. Res Commun Chem Pathol Pharmacol 36, 17–31.PubMedGoogle Scholar
  2. Ahkong, Q.F., Tilcock, C.,1992. Attachment of 99mTc to lipid vesicles containing the lipophilic chelate dipalmitoylphosphatidylethanolamine-DTTA. Int J Rad Appl Instrum B 19, 831–840.PubMedGoogle Scholar
  3. Alafandy, M., Goffinet, G., Umbrain, V., D’Haese, J., Camu, F., Legros, F.J.,1996. 99mTechnetium-stannous oxinate as marker of liposome formulations. Nucl Med Biol 23, 881–887.PubMedCrossRefGoogle Scholar
  4. Allen, T.M., Hansen, C., Martin, F., Redemann, C., Yau-Young, A.,1991. Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim Biophys Acta 1066, 29–36.PubMedCrossRefGoogle Scholar
  5. Bao, A., Goins, B., Klipper, R., Negrete, G., Mahindaratne, M., Phillips, W.T.,2003. A novel liposome radiolabeling method using 99mTc-“SNS/S” complexes: in vitro and in vivo evaluation. J Pharm Sci 92, 1893–1904.PubMedCrossRefGoogle Scholar
  6. Bao, A., Goins, B., Klipper, R., Negrete, G., Phillips, W.T.,2004. Direct 99mTc labeling of pegylated liposomal doxorubicin (Doxil) for pharmacokinetic and non-invasive imaging studies. J Pharmacol Exp Ther 308, 419–425.PubMedCrossRefGoogle Scholar
  7. Barenholz, Y., Amselem, S., Goren, D., Cohen, R., Gelvan, D., Samuni, A., Golden, E.B., Gabizon, A.,1993. Stability of liposomal doxorubicin formulations: problems and prospects. Med Res Rev 13, 449–491.PubMedCrossRefGoogle Scholar
  8. Beaumier, P.L., Hwang, K.J., Slattery, J.T.,1983. Effect of liposome dose on the elimination of small unilamellar sphingomyelin/cholesterol vesicles from the circulation. Res Commun Chem Pathol Pharmacol 39, 277–289.PubMedGoogle Scholar
  9. Belhaj-Tayeb, H., Briane, D., Vergote, J., Kothan, S., Leger, G., Bendada, S.E., Tofighi, M., Tamgac, F., Cao, A., Moretti, J.L.,2003. In vitro and in vivo study of 99mTc-MIBI encapsulated in PEG-liposomes: a promising radiotracer for tumour imaging. Eur J Nucl Med Mol Imaging 30, 502–509.PubMedCrossRefGoogle Scholar
  10. Blume, G., Cevc, G., Crommelin, M.D., Bakker-Woudenberg, I.A., Kluft, C., Storm, G.,1993. Specific targeting with poly(ethylene glycol)-modified liposomes: coupling of homing devices to the ends of the polymeric chains combines effective target binding with long circulation times. Biochim Biophys Acta 1149, 180–184.PubMedCrossRefGoogle Scholar
  11. Boerman, O.C., Laverman, P., Oyen, W.J., Corstens, F.H., Storm, G.,2000. Radiolabeled liposomes for scintigraphic imaging. Prog Lipid Res 39, 461–475.PubMedCrossRefGoogle Scholar
  12. Bosworth, M.E., Hunt, C.A.,1982. Liposome disposition in vivo II: Dose dependency. J Pharm Sci 71, 100–104.PubMedCrossRefGoogle Scholar
  13. Caride, V.J., Taylor, W., Cramer, J.A., Gottschalk, A., 1976. Evaluation of liposome-entrapped radioactive tracers as scanning agents. Part 1: Organ distribution of liposome (99mTc-DTPA) in mice. J Nucl Med 17, 1067–1072.PubMedGoogle Scholar
  14. Chakilam, A.R., Pabba, S., Mongayt, D., Iakoubov, L.Z., Torchilin, V.P., 2004. A single monoclonal antinuclear autoantibody with nucleosome-restricted specificity inhibits the growth of diverse human tumors in nude mice. Cancer Therapy 2, 353–364.Google Scholar
  15. Cheung, T.W., Remick, S.C., Azarnia, N., Proper, J.A., Barrueco, J.R., Dezube, B.J.,1999. AIDS-related Kaposi’s sarcoma: a phase II study of liposomal doxorubicin. The TLC D-99 Study Group. Clin Cancer Res 5, 3432–3437.PubMedGoogle Scholar
  16. Dagar, S., Krishnadas, A., Rubinstein, I., Blend, M.J., Onyuksel, H.,2003. VIP grafted sterically stabilized liposomes for targeted imaging of breast cancer: in vivo studies. J Control Release 91, 123–133.PubMedCrossRefGoogle Scholar
  17. Damen, J., Regts, J., Scherphof, G.,1981. Transfer and exchange of phospholipid between small unilamellar liposomes and rat plasma high density lipoproteins. Dependence on cholesterol content and phospholipid composition. Biochim Biophys Acta 665, 538–545.PubMedGoogle Scholar
  18. Elbayoumi, T.A., Torchilin, V.P.,2006. Enhanced accumulation of long-circulating liposomes modified with the nucleosome-specific monoclonal antibody 2C5 in various tumours in mice: gamma-imaging studies. Eur J Nucl Med Mol Imaging 33, 1196–1205.PubMedCrossRefGoogle Scholar
  19. Erdogan, S., Roby, A., Sawant, R., Hurley, J., Torchilin, V.P., 2006a. Gadolinium-loaded polychelating polymer-containing cancer cell-specific immunoliposomes. J Liposome Res 16, 45–55.CrossRefGoogle Scholar
  20. Erdogan, S., Roby, A., Torchilin, V.P., 2006b. Enhanced tumor visualization by gamma scintigraphy with 111In-labeled polychelating polymer-containing immunoliposomes. Molecular Pharmaceutics. (In press).Google Scholar
  21. Gabizon, A.A.,1995. Liposome circulation time and tumor targeting: implications for cancer therapy. Adv Drug Deliv Rev 16, 285–294.CrossRefGoogle Scholar
  22. Gabizon, A.A., Lyass, O., Berry, G.J., Wildgust, M.,2004. Cardiac safety of pegylated liposomal doxorubicin (Doxil/Caelyx) demonstrated by endomyocardial biopsy in patients with advanced malignancies. Cancer Invest 22, 663–669.PubMedCrossRefGoogle Scholar
  23. Gabizon, A., Huberty, J., Straubinger, R.M., Price, D.C., Papahadjopoulos, D.,1988. An improved method for in vivo tracking and imaging of liposomes using a gallium-67deferoxamine complex. J Liposome Res 1, 123–135.CrossRefGoogle Scholar
  24. Gabizon, A., Price, D.C., Huberty, J., Bresalier, R.S., Papahadjopoulos, D., 1990. Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies. Cancer Res. 50: 6371–6378.PubMedGoogle Scholar
  25. Gabizon, A., Shmeeda, H., Barenholz, Y.,2003. Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin Pharmacokinet 42, 419–436.PubMedCrossRefGoogle Scholar
  26. Goins, B., Klipper, R., Rudolph, A.S., Phillips, W.T.,1994. Use of technetium-99mliposomes in tumor imaging. J Nucl Med 35, 1491–1498.PubMedGoogle Scholar
  27. Goins, B.A., Phillips, W.T.,2001. The use of scintigraphic imaging as a tool in the development of liposome formulations. Prog Lipid Res 40, 95–123.PubMedCrossRefGoogle Scholar
  28. Goins, B., Phillips, T.,2003. Radiolabeled liposomes for imaging and biodistribution studies. In: Liposomes: A Practical Approach, Vol. 1, eds V. Torchilin, V. Weissig, 2nd edn, pp. 319–336. Oxford University Press, London.Google Scholar
  29. Goto, R., Kubo, H., Okada, S.,1989. Liposomes prepared from synthetic amphiphiles. I. Their technetium labeling and stability. Chem Pharm Bull (Tokyo) 37, 1351–1354.Google Scholar
  30. Gregoriadis, G., Neerunjun, D.E.,1974. Control of the rate of hepatic uptake and catabolism of liposome-entrapped proteins injected into rats. Possible therapeutic applications. Eur J Biochem 47, 179–185.PubMedCrossRefGoogle Scholar
  31. Gregoriadis, G., Putman, D., Louis, L., Neerunjun, D., 1974a. Comparative effect and fate of non-entrapped and liposome-entrapped neuraminidase injected into rats. Biochem J 140, 323–330.Google Scholar
  32. Gregoriadis, G., Wills, E.J., Swain, C.P., Tavill, A.S., 1974b. Drug-carrier potential of liposomes in cancer chemotherapy. Lancet 1, 1313–1316.CrossRefGoogle Scholar
  33. Gupta, B., Levchenko, T.S., Mongayt, D.A., Torchilin, V.P.,2005. Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in vitro and in subcutaneous tumor model in vivo. J Drug Target 13, 337–343.PubMedCrossRefGoogle Scholar
  34. Harrington, K.J., Lewanski, C., Northcote, A.D., Whittaker, J., Peters, A.M., Vile, R.G., Stewart, J.S., 2001a. Phase II study of pegylated liposomal doxorubicin (Caelyx) as induction chemotherapy for patients with squamous cell cancer of the head and neck. Eur J Cancer 37, 2015–2022.CrossRefGoogle Scholar
  35. Harrington, K.J., Mohammadtaghi, S., Uster, P.S., Glass, D., Peters, A.M., Vile, R.G., Stewart, J.S., 2001b. Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res 7, 243–254.Google Scholar
  36. Harrington, K.J., Rowlinson-Busza, G., Syrigos, K.N., Abra, R.M., Uster, P.S., Peters, A.M., Stewart, J.S., 2000a. Influence of tumour size on uptake of(111)ln-DTPA-labelled pegylated liposomes in a human tumour xenograft model. Br J Cancer 83, 684–688.CrossRefGoogle Scholar
  37. Harrington, K.J., Rowlinson-Busza, G., Syrigos, K.N., Uster, P.S., Abra, R.M., Stewart, J.S., 2000b. Biodistribution and pharmacokinetics of 111In-DTPA-labelled11. Use of Radiolabeled Liposomes for Tumor Imaging 233 pegylated liposomes in a human tumour xenograft model: implications for novel targeting strategies. Br J Cancer 83, 232–238.CrossRefGoogle Scholar
  38. Harrington, K.J., Rowlinson-Busza, G., Syrigos, K.N., Uster, P.S., Vile, R.G., Stewart, J.S., 2000c. Pegylated liposomes have potential as vehicles for intratumoral and subcutaneous drug delivery. Clin Cancer Res 6, 2528–2537.Google Scholar
  39. Herschman, H.R., MacLaren, D.C., Iyer, M., Namavari, M., Bobinski, K., Green, L.A., Wu, L., Berk, A.J., Toyokuni, T., Barrio, J.R., Cherry, S.R., Phelps, M.E., Sandgren, E.P., Gambhir, S.S.,2000. Seeing is believing: non-invasive, quantitative and repetitive imaging of reporter gene expression in living animals, using positron emission tomography. J Neurosci Res 59, 699–705.PubMedCrossRefGoogle Scholar
  40. Hnatowich, D.J., Friedman, B., Clancy, B., Novak, M.,1981. Labeling of preformed liposomes with Ga-67 and Tc-99m by chelation. J Nucl Med 22, 810–814.PubMedGoogle Scholar
  41. Huang, S.K., Mayhew, E., Gilani, S., Lasic, D.D., Martin, F.J., Papahadjopoulos, D.,1992. Pharmacokinetics and therapeutics of sterically stabilized liposomes in mice bearing C-26 colon carcinoma. Cancer Res 52, 6774–6781.PubMedGoogle Scholar
  42. Hwang, K.J., Merriam, J.E., Beaumier, P.L., Luk, K.F.,1982. Encapsulation, with high efficiency, of radioactive metal ions in liposomes. Biochim Biophys Acta 716, 101–109.PubMedGoogle Scholar
  43. Iakoubov, L.Z., Torchilin, V.P.,1997. A novel class of antitumor antibodies: nucleosome-restricted antinuclear autoantibodies (ANA) from healthy aged nonautoimmune mice. Oncol Res 9, 439–446.PubMedGoogle Scholar
  44. Ishida, O., Maruyama, K., Sasaki, K., Iwatsuru, M.,1999. Size-dependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice. Int J Pharm 190, 49–56.PubMedCrossRefGoogle Scholar
  45. Jaggi, M., Khar, R., Chauhan, U., Gangal, S.,1991. Liposomes as carriers of technetium99m glucoheptonate for liver imaging. Int J Pharm 69, 77–79.CrossRefGoogle Scholar
  46. Janoff, A.S.,1992. Lipids, liposomes, and rational drug design. Lab Invest 66, 655–658.PubMedGoogle Scholar
  47. Kabalka, G.W., Davis, M.A., Moss, T.H., Buonocore, E., Hubner, K., Holmberg, E., Maruyama, K., Huang, L.,1991. Gadolinium-labeled liposomes containing various amphiphilic Gd-DTPA derivatives: targeted MRI contrast enhancement agents for the liver. Magn Reson Med 19, 406–415.PubMedCrossRefGoogle Scholar
  48. Khalifa, A., Dodds, D., Rampling, R., Paterson, J., Murray, T.,1997. Liposomal distribution in malignant glioma: possibilities for therapy. Nucl Med Commun 18, 17–23.PubMedCrossRefGoogle Scholar
  49. Khaw, B.A., Klibanov, A., O’Donnell, S.M., Saito, T., Nossiff, N., Slinkin, M.A., Newell, J.B., Strauss, H.W., Torchilin, V.P.,1991. Gamma imaging with negatively charge-modified monoclonal antibody: modification with synthetic polymers. J Nucl Med 32, 1742–1751.PubMedGoogle Scholar
  50. Kirby, C., Clarke, J., Gregoriadis, G., 1980a. Cholesterol content of small unilamellar liposomes controls phospholipid loss to high density lipoproteins in the presence of serum. FEBS Lett 111, 324–328.CrossRefGoogle Scholar
  51. Kirby, C., Clarke, J., Gregoriadis, G., 1980b. Effect of the cholesterol content of small unilamellar liposomes on their stability in vivo and in vitro. Biochem J 186, 591–598.Google Scholar
  52. Klibanov, A.L., Maruyama, K., Torchilin, V.P., Huang, L.,1990. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett 268, 235–237.PubMedCrossRefGoogle Scholar
  53. Koukourakis, M.I., Koukouraki, S., Fezoulidis, I., Kelekis, N., Kyrias, G., Archimandritis, S., Karkavitsas, N., 2000a. High intratumoural accumulation of stealth liposomal doxorubicin (Caelyx) in glioblastomas and in metastatic brain tumours. Br J Cancer 83, 1281–1286.CrossRefGoogle Scholar
  54. Koukourakis, M.I., Koukouraki, S., Giatromanolaki, A., Archimandritis, S.C., Skarlatos, J., Beroukas, K., Bizakis, J.G., Retalis, G., Karkavitsas, N., Helidonis, E.S.,1999. Liposomal doxorubicin and conventionally fractionated radiotherapy in the treatment of locally advanced non-small-cell lung cancer and head and neck cancer. J Clin Oncol 17, 3512–3521.PubMedGoogle Scholar
  55. Koukourakis, M.I., Koukouraki, S., Giatromanolaki, A., Kakolyris, S., Georgoulias, V., Velidaki, A., Archimandritis, S., Karkavitsas, N.N., 2000b. High intratumoral accumulation of stealth liposomal doxorubicin in sarcomas–rationale for combination with radiotherapy. Acta Oncol 39, 207–211.CrossRefGoogle Scholar
  56. Lasch, J., Weissig, V., Brandl, M.,2003. Preparation of liposomes. In: Liposomes: A Practical Approach, eds V. P. Torchilin, V. Weissig, 2nd edn, pp. 3–29. Oxford University Press, Oxford, New York.Google Scholar
  57. Lasic, D.D.,1993. Liposomes from physics to applications, 1st edn. Elsevier Science publishers, Amsterdam.Google Scholar
  58. Lasic, D.D., Martin, F., eds, 1995. Stealth liposomes. CRC Press, Boca Raton.Google Scholar
  59. Lasic, D.D., Papahadjopoulos, D., eds, 1998. Medical applications of liposomes. Elsevier, New York.Google Scholar
  60. Laverman, P., Dams, E.T., Oyen, W.J., Storm, G., Koenders, E.B., Prevost, R., van der Meer, J.W., Corstens, F.H., Boerman, O.C.,1999. A novel method to label liposomes with 99mTc by the hydrazino nicotinyl derivative. J Nucl Med 40, 192–197.PubMedGoogle Scholar
  61. Laverman, P., Zalipsky, S., Oyen, W.J., Dams, E.T., Storm, G., Mullah, N., Corstens, F.H., Boerman, O.C.,2000. Improved imaging of infections by avidin-induced clearance of 99mTc-biotin-PEG liposomes. J Nucl Med 41, 912–918.PubMedGoogle Scholar
  62. Love, W.G., Amos, N., Williams, B.D., Kellaway, I.W.,1989. Effect of liposome surface charge on the stability of technetium (99mTc) radiolabelled liposomes. J Microencapsul 6, 105–113.PubMedCrossRefGoogle Scholar
  63. Lukyanov, A.N., Elbayoumi, T.A., Chakilam, A.R., Torchilin, V.P.,2004. Tumor-targeted liposomes: doxorubicin-loaded long-circulating liposomes modified with anti-cancer antibody. J Control Release 100, 135–144.PubMedCrossRefGoogle Scholar
  64. Maeda, H.,2001. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 41, 189–207.PubMedCrossRefGoogle Scholar
  65. Maeda, H., Wu, J., Sawa, T., Matsumura, Y., Hori, K.,2000. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65, 271–284.PubMedCrossRefGoogle Scholar
  66. Morgan, J.R., Williams, K.E., Davies, R.L., Leach, K., Thomson, M., Williams, L.A.,1981. Localisation of experimental staphylococcal abscesses by 99MTC-technetiumlabelled liposomes. J Med Microbiol 14, 213–217.PubMedCrossRefGoogle Scholar
  67. Mori, A., Klibanov, A.L., Torchilin, V.P., Huang, L.,1991. Influence of the steric barrier activity of amphipathic poly(ethyleneglycol) and ganglioside GM1 on the circulation time of liposomes and on the target binding of immunoliposomes in vivo. FEBS Lett 284, 263–266.PubMedCrossRefGoogle Scholar
  68. Noguchi, Y., Wu, J., Duncan, R., Strohalm, J., Ulbrich, K., Akaike, T., Maeda, H.,1998. Early phase tumor accumulation of macromolecules: a great difference in clearance rate between tumor and normal tissues. Jpn J Cancer Res 89, 307–314.PubMedGoogle Scholar
  69. Ogihara-Umeda, I., Sasaki, T., Nishigori, H.,1992. Development of a liposome-encapsulated radionuclide with preferential tumor accumulation–the choice of radionuclide and chelating ligand. Int J Rad Appl Instrum B 19, 753–757.PubMedGoogle Scholar
  70. Ogihara-Umeda, I., Sasaki, T., Nishigori, H.,1993. Active removal of radioactivity in the blood circulation using biotin-bearing liposomes and avidin for rapid tumour imaging. Eur J Nucl Med 20, 170–172.PubMedCrossRefGoogle Scholar
  71. Oku, N., 1999. Delivery of contrast agents for positron emission tomography imaging by liposomes. Adv Drug Deliv Rev 37, 53–61.PubMedCrossRefGoogle Scholar
  72. Papahadjopoulos, D.,1988. Liposome formation and properties: an evolutionary profile. Biochem Soc Trans 16, 910–912.PubMedGoogle Scholar
  73. Papahadjopoulos, D., Allen, T.M., Gabizon, A., Mayhew, E., Matthay, K., Huang, S.K., Lee, K.D., Woodle, M.C., Lasic, D.D., Redemann, C., Martin, F.J.,1991. Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad SciUSA88, 11460–11464.CrossRefGoogle Scholar
  74. Patel, H.M., Boodle, K.M., Vaughan-Jones, R.,1984. Assessment of the potential uses of liposomes for lymphoscintigraphy and lymphatic drug delivery. Failure of 99mtechnetium marker to represent intact liposomes in lymph nodes. Biochim Biophys Acta 801, 76–86.PubMedGoogle Scholar
  75. Philippot, J.R., Puyal, C.O.,1995. In: Liposomes, New Systems and New Trends in Their Application, Vol. 1, eds F. Puisieux, P. Couvreur, J. Delattre, J. P. Devissaguet, pp. 193–215. Editions de Sante, Paris.Google Scholar
  76. Phillips, T.W., Goins, B.,1995. Targeted delivery of imaging agents by liposomes. In: Handbook of targeted delivery of imaging agents, ed V. P. Torchilin. CRS Press, Boca Raton.Google Scholar
  77. Phillips, W.T.,1999. Delivery of gamma-imaging agents by liposomes. Adv Drug Deliv Rev 37, 13–32.PubMedCrossRefGoogle Scholar
  78. Phillips, W.T., Rudolph, A.S., Goins, B., Timmons, J.H., Klipper, R., Blumhardt, R.,1992. A simple method for producing a technetium-99m-labeled liposome which is stable in vivo. Int J Rad Appl Instrum B 19 539–547.PubMedGoogle Scholar
  79. Presant, C.A., Blayney, D., Proffitt, R.T., Turner, A.F., Williams, L.E., Nadel, H.I., Kennedy, P., Wiseman, C., Gala, K., Crossley, R.J., et al., 1990. Preliminary report: imaging of Kaposi sarcoma and lymphoma in AIDS with indium-111-labelled liposomes. Lancet 335, 1307–1309.PubMedCrossRefGoogle Scholar
  80. Proffitt, R.T., Williams, L.E., Presant, C.A., Tin, G.W., Uliana, J.A., Gamble, R.C., Baldeschwieler, J.D.,1983. Tumor-imaging potential of liposomes loaded with In-111NTA: biodistribution in mice. J Nucl Med 24, 45–51.PubMedGoogle Scholar
  81. Richardson, V.J., Ryman, B.E., Jewkes, R.F., Jeyasingh, K., Tattersall, M.N., Newlands, E.S., Kaye, S.B.,1979. Tissue distribution and tumour localization of 99mtechnetium-labelled liposomes in cancer patients. Br J Cancer 40, 35–43.PubMedGoogle Scholar
  82. Senior, J., Crawley, J.C., Gregoriadis, G.,1985. Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection. Biochim Biophys Acta 839, 1–8.PubMedGoogle Scholar
  83. Senior, J., Gregoriadis, G.,1982. Stability of small unilamellar liposomes in serum and clearance from the circulation: the effect of the phospholipid and cholesterol components. Life Sci 30, 2123–2136.PubMedCrossRefGoogle Scholar
  84. Senior, J.H.,1987. Fate and behavior of liposomes in vivo: a review of controlling factors. Crit Rev Ther Drug Carrier Syst 3, 123–193.PubMedGoogle Scholar
  85. Slinkin, M.A., Klibanov, A.L., Torchilin, V.P.,1991. Terminal-modified polylysine-based chelating polymers: highly efficient coupling to antibody with minimal loss in immunoreactivity. Bioconjug Chem 2, 342–348.PubMedCrossRefGoogle Scholar
  86. Strauss, L.G.,1997. Positron emission tomography: Current role for diagnosis and therapy monitoring in oncology. Oncologist 2, 381–388.PubMedGoogle Scholar
  87. Suresh, M., Cao, Y.,1998. A simple and efficient method for radiolabeling of preformed liposomes. J Pharm Pharm Sci 1, 31–37.PubMedGoogle Scholar
  88. Swenson, C.E., Bolcsak, L.E., Batist, G., Guthrie, T.H., Jr., Tkaczuk, K.H., Boxenbaum, H., Welles, L., Chow, S.C., Bhamra, R., Chaikin, P.,2003. Pharmacokinetics of doxorubicin administered i.v. as Myocet (TLC D-99; liposome-encapsulated doxorubicin citrate) compared with conventional doxorubicin when given in combination with cyclophosphamide in patients with metastatic breast cancer. Anticancer Drugs 14, 239–246.PubMedCrossRefGoogle Scholar
  89. Torchilin, V.P.,1994. Immunoliposomes and PEGylated immunoliposomes: possible use for targeted delivery of imaging agents. Immunomethods 4, 244–258.PubMedCrossRefGoogle Scholar
  90. Torchilin, V.P., ed1995. Handbook of targeted delivery of imaging agents. CRS Press, Boca Raton.Google Scholar
  91. Torchilin, V.P.,1996. Liposomes as delivery agents for medical imaging. Mol Med Today 2, 242–249.PubMedCrossRefGoogle Scholar
  92. Torchilin, V.P.,1997. Pharmacokinetic considerations in the development of labeled liposomes and micelles for diagnostic imaging. Q J Nucl Med 41, 141–153.PubMedGoogle Scholar
  93. Torchilin, V.P., 2000a. Drug targeting. Eur J Pharm Sci 11 Suppl 2, S81–S91.CrossRefGoogle Scholar
  94. Torchilin, V.P., 2000b. Polymeric contrast agents for medical imaging. Curr Pharm Biotechnol 1, 183–215.CrossRefGoogle Scholar
  95. Torchilin, V.P.,2005. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4, 145–160.PubMedCrossRefGoogle Scholar
  96. Torchilin, V.P., Klibanov, A.L.,1991. The antibody-linked chelating polymers for nuclear therapy and diagnostics. Crit Rev Ther Drug Carrier Syst 7, 275–308.PubMedGoogle Scholar
  97. Torchilin, V.P., Lukyanov, A.N., Gao, Z., Papahadjopoulos-Sternberg, B., 2003. Immunomicelles: Targeted pharmaceutical carriers for poorly soluble drugs. Proc Natl Acad SciUSA 100, 6039–6044.CrossRefGoogle Scholar
  98. Torchilin, V.P., Omelyanenko, V.G., Papisov, M.I., Bogdanov, A.A., Jr., Trubetskoy, V.S., Herron, J.N., Gentry, C.A.,1994. Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity. Biochim Biophys Acta 1195, 11–20.PubMedCrossRefGoogle Scholar
  99. Torchilin, V.P., Trubetskoy, V.S., 1995a. In vivo visualizing of organs and tissues with liposomes. J Liposome Research 5, 795–812.CrossRefGoogle Scholar
  100. Torchilin, V.P., Trubetskoy, V.S., 1995b. Which polymers can make nanoparticulate drug carriers long-circulating? Adv Drug Deliv Rev 16, 141–155.Google Scholar
  101. Torchilin, V.P., Weissig, V.,2003. Liposomes: a practical approach. 2nd edn. Oxford University Press, Oxford, New York.Google Scholar
  102. Tulpule, A., Yung, R.C., Wernz, J., Espina, B.M., Myers, A., Scadden, D.T., Cabriales, S., Ilaw, M., Boswell, W., Gill, P.S.,1998. Phase II trial of liposomal daunorubicin in the treatment of AIDS-related pulmonary Kaposi’s sarcoma. J Clin Oncol 16, 3369–3374.PubMedGoogle Scholar
  103. Wolf, G.L.,1995. Targeted delivery of imaging agents: An over view. In: Handbook of targeted delivery of imaging agents, ed V.P. Torchilin. CRS Press, Boca Raton.Google Scholar
  104. Yuan, F., Leunig, M., Huang, S.K., Berk, D.A., Papahadjopoulos, D., Jain, R.K.,1994. Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res 54, 3352–3356.PubMedGoogle Scholar
  105. Zheng, J.G., Tan, T.Z.,2004. Antisense imaging of colon cancer-bearing nude mice with liposome-entrapped 99m-technetium-labeled antisense oligonucleotides of c-myc mRNA. World J Gastroenterol 10, 2563–2566.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Tamer Elbayoumi
  • Vladimir Torchilin

There are no affiliations available

Personalised recommendations