Nanoparticles for Pancreatic Islet Imaging

Part of the Biosystems & Biorobotics book series (BIOSYSROB, volume 9)


While clinical islet transplantation is being investigated as a useful method to cure diabetes mellitus (DM), the outcome of this therapy remains imperfect. This is mainly due to early graft rejection of transplanted islets by the instant blood-mediated inflammatory reaction (IBMIR) or islet ischemia. Therefore, it is important to develop imaging tools for transplanted islets, so that real-time treatment can be used to protect the islets from host immune reactions if required. Recently, synthetic nanoparticles are emerging in the area of biomedical imaging. Innovative nanoparticle developments have significantly enhanced the versatility of different imaging modalities. Nanoparticles represent potential probes to monitor transplanted islets through magnetic resonance imaging (MRI), positron emission tomography (PET), and optical imaging. Nanoparticles can be delivered to transplanted islets by conjugation onto the cell membrane, intracellular delivery, cellular membrane receptor or transporter targeting. Visualizing the survival, function, and biodistribution of transplanted islets may suggest an appropriate treatment, which will enhance islet graft survival. This chapter focuses on recent advances and applications of various nanoparticle-based imaging techniques used in molecular imaging to monitor transplanted islets.


Nanoparticle Islet Diabetes Transplantation MRI PET 


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  1. 1.
    Andersen, D.K.: The practical importance of recognizing pancreatogenic or type 3c diabetes. Diabetes-Metab. Res. 28, 326–328 (2012)CrossRefGoogle Scholar
  2. 2.
    Ewald, N., Kaufmann, C., Raspe, A., Kloer, H.U., Bretzel, R.G., Hardt, P.D.: Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c). Diabetes-Metab. Res. 28, 338–342 (2012)CrossRefGoogle Scholar
  3. 3.
    Ricordi, C., Strom, T.B.: Clinical islet transplantation: Advances and immunological challenges. Nat. Rev. Immunol. 4, 258–268 (2004)CrossRefGoogle Scholar
  4. 4.
    Ryan, E.A., Paty, B.W., Senior, P.A., Bigam, D., Alfadhli, E., Kneteman, N.M., et al.: Five-year follow-up after clinical islet transplantation. Diabetes 54, 2060–2069 (2005)CrossRefGoogle Scholar
  5. 5.
    Sakata, N., Hayes, P., Tan, A., Chan, N.K., Mace, J., Peverini, R., et al.: MRI Assessment of Ischemic Liver After Intraportal Islet Transplantation. Transplantation 87, 825–830 (2009)CrossRefGoogle Scholar
  6. 6.
    Johansson, H., Lukinius, A., Moberg, L., Lundgren, T., Berne, C., Foss, A., et al.: Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation. Diabetes 54, 1755–1762 (2005)CrossRefGoogle Scholar
  7. 7.
    Shapiro, A.M.J., Ricordi, C., Hering, B.J., Auchincloss, H., Lindblad, R., Robertson, P., et al.: International trial of the edmonton protocol for islet transplantation. New Engl. J. Med. 355, 1318–1330 (2006)CrossRefGoogle Scholar
  8. 8.
    Shapiro, A.M.J., Lakey, J.R.T., Ryan, E.A., Korbutt, G.S., Toth, E., Warnock, G.L., et al.: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. New Engl. J. Med. 343, 230–238 (2000)CrossRefGoogle Scholar
  9. 9.
    Ayres, R.C.S., Dousset, B., Wixon, S., Buckels, J.A.C., Mcmaster, P., Mayer, A.D.: Peripheral Neurotoxicity with Tacrolimus. Lancet 343, 862–863 (1994)CrossRefGoogle Scholar
  10. 10.
    Berthoux, F.: European best practice guidelines for renal transplantation (Part 2) - Preface. Nephrol. Dial. Transpl. 17, 2 (2002)Google Scholar
  11. 11.
    Pascual, M., Theruvath, T., Kawai, T., Tolkoff-Rubin, N., Cosimi, A.B.: Medical progress - Strategies to improve long-term outcomes after renal transplantation. New Engl. J. Med. 346, 580–590 (2002)CrossRefGoogle Scholar
  12. 12.
    Radu, R.G., Fujimoto, S., Mukai, E., Takehiro, M., Shimono, D., Nabe, K., et al.: Tacrolimus suppresses glucose-induced insulin release from pancreatic islets by reducing glucokinase activity. Am. J. Physiol-Endoc. M. 288, E365–E371 (2005)Google Scholar
  13. 13.
    Desai, N.M., Goss, J.A., Deng, S.P., Wolf, B.A., Markmann, E., Palanjian, M., et al.: Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant recipients: Local immunosuppression or islet toxicity? Transplantation 76, 1623–1625 (2003)CrossRefGoogle Scholar
  14. 14.
    Shivaswamy, V., McClure, M., Passer, J., Frahm, C., Ochsner, L., Erickson, J., et al.: Hyperglycemia induced by tacrolimus and sirolimus is reversible in normal sprague-dawley rats. Endocrine 37, 489–496 (2010)CrossRefGoogle Scholar
  15. 15.
    Lu, Y.X., Dang, H., Middleton, B., Zhang, Z., Washburn, L., Campbell-Thompson, M., et al.: Bioluminescent monitoring of islet graft survival after transplantation. Mol. Ther. 9, 428–435 (2004)CrossRefGoogle Scholar
  16. 16.
    Chen, X.J., Zhang, X.M., Larson, C.S., Baker, M.S., Kaufman, D.B.: In vivo bioluminescence imaging of transplanted islets and early detection of graft rejection. Transplantation 81, 1421–1427 (2006)CrossRefGoogle Scholar
  17. 17.
    Virostko, J., Radhika, A., Poffenberger, G., Chen, Z.Y., Brissova, M., Gilchrist, J., et al.: Bioluminescence Imaging in Mouse Models Quantifies beta Cell Mass in the Pancreas and After Islet Transplantation. Mol. Imaging Biol. 12, 42–53 (2010)CrossRefGoogle Scholar
  18. 18.
    Massoud, T.F., Gambhir, S.S.: Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Gene Dev. 17, 545–580 (2003)CrossRefGoogle Scholar
  19. 19.
    Jirak, D., Kriz, J., Herynek, V., Andersson, B., Girman, P., Burian, M., et al.: MRI of transplanted pancreatic islets. Magnet Reson. Med. 52, 1228–1233 (2004)CrossRefGoogle Scholar
  20. 20.
    Toso, C., Zaidi, H., Morel, P., Armanet, M., Andres, A., Pernin, N., et al.: Positron-emission tomography imaging of early events after transplantation of islets of Langerhans. Transplantation 79, 353–355 (2005)CrossRefGoogle Scholar
  21. 21.
    Lu, Y.X., Dang, H., Middleton, B., Campbell-Thompson, M., Atkinson, M.A., Gambhir, S.S., et al.: Long-term monitoring of transplanted islets using positron emission tomography. Mol. Ther. 14, 851–856 (2006)CrossRefGoogle Scholar
  22. 22.
    Yang, B., Cai, H.L., Qin, W.J., Zhang, B., Zhai, C.X., Jiang, B., et al.: Bcl-2-functionalized ultrasmall superparamagnetic iron oxide nanoparticles coated with amphiphilic polymer enhance the labeling efficiency of islets for detection by magnetic resonance imaging. International Journal of Nanomedicine 8, 3977–3990 (2013)Google Scholar
  23. 23.
    Evgenov, N.V., Medarova, Z., Dai, G., Bonner-Weir, S., Moore, A.: In vivo imaging of islet transplantation. Nature Medicine 12, 144–148 (2006)CrossRefGoogle Scholar
  24. 24.
    Jiao, Y., Peng, Z.H., Zhang, J.Y., Qin, J., Zhong, C.P.: Liposome-Mediated Transfer Can Improve the Efficacy of Islet Labeling With Superparamagnetic Iron Oxide. Transpl P. 40, 3615–3618 (2008)Google Scholar
  25. 25.
    Juang, J.H., Wang, J.J., Shen, C.R., Kuo, C.H., Chien, Y.W., Kuo, H.Y., et al.: Magnetic Resonance Imaging of Transplanted Mouse Islets Labeled With Chitosan-Coated Superparamagnetic Iron Oxide Nanoparticles. Transpl. P. 42, 2104–2108 (2010)Google Scholar
  26. 26.
    Zhang, S.Z., He, H.J., Lu, W.W., Xu, Q.J., Zhou, B.J., Tang, X.D.: Tracking Intrahepatically Transplanted Islets Labeled With Feridex-Polyethyleneimine Complex Using a Clinical 3.0-T Magnetic Resonance Imaging Scanner. Pancreas 38, 293–302 (2009)CrossRefGoogle Scholar
  27. 27.
    Huber, D.L.: Synthesis, properties, and applications of iron nanoparticles. Small 1, 482–501 (2005)CrossRefGoogle Scholar
  28. 28.
    Ito, A., Shinkai, M., Honda, H., Kobayashi, T.: Medical application of functionalized magnetic nanoparticles. Journal of Bioscience and Bioengineering 100, 1–11 (2005)CrossRefGoogle Scholar
  29. 29.
    Elias, A., Tsourkas, A.: Imaging circulating cells and lymphoid tissues with iron oxide nanoparticles. Hematology / the Education Program of the American Society of Hematology American Society of Hematology Education Program, 720–726 (2009)Google Scholar
  30. 30.
    Chemically prepared magnetic nanoparticles. International Materials Reviews 49, 125–170 (2004)Google Scholar
  31. 31.
    Hwang, Y.H., Lee, D.Y.: Magnetic resonance imaging using heparin-coated superparamagnetic iron oxide nanoparticles for cell tracking in vivo. Quantitative Imaging in Medicine and Surgery 2, 118–123 (2012)Google Scholar
  32. 32.
    Sun, C., Lee, J.S., Zhang, M.: Magnetic nanoparticles in MR imaging and drug delivery. Adv. Drug Deliv. Rev. 60, 1252–1265 (2008)CrossRefGoogle Scholar
  33. 33.
    McCarthy, J.R., Weissleder, R.: Multifunctional magnetic nanoparticles for targeted imaging and therapy. Adv. Drug Deliv. Rev. 60, 1241–1251 (2008)CrossRefGoogle Scholar
  34. 34.
    Laurent, S., Forge, D., Port, M., Roch, A., Robic, C., Vander Elst, L., et al.: Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chemical Reviews 108, 2064–2110 (2008)CrossRefGoogle Scholar
  35. 35.
    Wang, Y.X., Hussain, S.M., Krestin, G.P.: Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. European Radiology 11, 2319–2331 (2001)CrossRefGoogle Scholar
  36. 36.
    Bonnemain, B.: Superparamagnetic agents in magnetic resonance imaging: physicochemical characteristics and clinical applications. A Review, Journal of Drug Targeting 6, 167–174 (1998)CrossRefGoogle Scholar
  37. 37.
    Harisinghani, M.G., Barentsz, J., Hahn, P.F., Deserno, W.M., Tabatabaei, S., van de Kaa, C.H., et al.: Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. The New England Journal of Medicine 348, 2491–2499 (2003)CrossRefGoogle Scholar
  38. 38.
    Singh, A., Patel, T., Hertel, J., Bernardo, M., Kausz, A., Brenner, L.: Safety of ferumoxytol in patients with anemia and CKD. American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation 52, 907–915 (2008)CrossRefGoogle Scholar
  39. 39.
    Ris, F., Lepetit-Coiffe, M., Meda, P., Crowe, L.A., Toso, C., Armanet, M., et al.: Assessment of human islet labeling with clinical grade iron nanoparticles prior to transplantation for graft monitoring by MRI. Cell Transplantation 19, 1573–1585 (2010)CrossRefGoogle Scholar
  40. 40.
    Veranth, J.M., Kaser, E.G., Veranth, M.M., Koch, M., Yost, G.S.: Cytokine responses of human lung cells (BEAS-2B) treated with micron-sized and nanoparticles of metal oxides compared to soil dusts. Particle and Fibre Toxicology 4, 2 (2007)CrossRefGoogle Scholar
  41. 41.
    Hafeli, U.O., Riffle, J.S., Harris-Shekhawat, L., Carmichael-Baranauskas, A., Mark, F., Dailey, J.P., et al.: Cell uptake and in vitro toxicity of magnetic nanoparticles suitable for drug delivery. Molecular Pharmaceutics 6, 1417–1428 (2009)CrossRefGoogle Scholar
  42. 42.
    Jeng, H.A., Swanson, J.: Toxicity of metal oxide nanoparticles in mammalian cells. Journal of Environmental Science and Health Part A, Toxic/Hazardous Substances & Environmental Engineering 41, 2699–2711 (2006)CrossRefGoogle Scholar
  43. 43.
    Hussain, S.M., Hess, K.L., Gearhart, J.M., Geiss, K.T., Schlager, J.J.: In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicology in Vitro: An International Journal Published in Association with BIBRA 19, 975–983 (2005)CrossRefGoogle Scholar
  44. 44.
    Frank, J.A., Miller, B.R., Arbab, A.S., Zywicke, H.A., Jordan, E.K., Lewis, B.K., et al.: Clinically applicable labeling of mammalian and stem cells by combining; Superparamagnetic iron oxides and transfection agents. Radiology 228, 480–487 (2003)CrossRefGoogle Scholar
  45. 45.
    Zhang, Z.L., van den Bos, E.J., Wielopolski, P.A., de Jong-Popijus, M., Duncker, D.J., Krestin, G.P.: High-resolution magnetic resonance imaging of iron-labeled myoblasts using a standard 1.5-T clinical scanner. Magn. Reson. Mater Phy. 17, 201–209 (2004)Google Scholar
  46. 46.
    Klepka, M.T., Nedelko, N., Greneche, J.M., Lawniczak-Jablonska, K., Demchenko, I.N., Slawska-Waniewska, A., et al.: Local atomic structure and magnetic ordering of iron in Fe-chitosan complexes. Biomacromolecules 9, 1586–1594 (2008)CrossRefGoogle Scholar
  47. 47.
    Laudenslager, M.J., Schiffman, J.D., Schauer, C.L.: Carboxymethyl Chitosan as a Matrix Material for Platinum, Gold, and Silver Nanoparticles. Biomacromolecules 9, 2682–2685 (2008)CrossRefGoogle Scholar
  48. 48.
    Zhang, J., Wang, Q., Wang, L., Wang, A.: Manipulated dispersion of carbon nanotubes with derivatives of chitosan. Carbon 45, 1917–1920 (2007)CrossRefGoogle Scholar
  49. 49.
    Yoksan, R., Akashi, M., Miyata, M., Chirachanchai, S.: Optimal gamma-ray dose and irradiation conditions for producing low-molecular-weight chitosan that retains its chemical structure. Radiat. Res. 161, 471–480 (2004)CrossRefGoogle Scholar
  50. 50.
    Tsai, Z.T., Wang, J.F., Kuo, H.Y., Shen, C.R., Wang, J.J., Yen, T.C.: In situ preparation of high relaxivity iron oxide nanoparticles by coating with chitosan: A potential MRI contrast agent useful for cell tracking. J. Magn. Magn. Mater. 322, 208–213 (2010)CrossRefGoogle Scholar
  51. 51.
    Kim, S.J., Nian, C.L., Widenmaier, S., McIntosh, C.H.S.: Glucose-dependent insulinotropic polypeptide-mediated up-regulation of beta-cell antiapoptotic Bcl-2 gene expression is coordinated by cyclic AMP (cAMP) response element binding protein (CREB) and cAMP-responsive CREB coactivator 2. Mol. Cell Biol. 28, 1644–1656 (2008)CrossRefGoogle Scholar
  52. 52.
    Iwahashi, H., Hanafusa, T., Eguchi, Y., Nakajima, H., Miyagawa, J., Itoh, N., et al.: Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: Inhibition by Bcl-2. Diabetologia 39, 530–536 (1996)CrossRefGoogle Scholar
  53. 53.
    Aguilar-Bryan, L., Clement, J.P., Gonzalez, G., Kunjilwar, K., Babenko, A., Bryan, J.: Toward understanding the assembly and structure of K-ATP channels. Physiol. Rev. 78, 227–245 (1998)Google Scholar
  54. 54.
    Proks, P., Reimann, F., Green, N., Gribble, F., Ashcroft, F.: Sulfonylurea stimulation of insulin secretion. Diabetes 51, S368–S376 (2002)CrossRefGoogle Scholar
  55. 55.
    Schwanstecher, M., Schwanstecher, C., Dickel, C., Chudziak, F., Moshiri, A., Panten, U.: Location of the Sulfonylurea Receptor at the Cytoplasmic Face of the Beta-Cell Membrane. Brit. J. Pharmacol. 113, 903–911 (1994)CrossRefGoogle Scholar
  56. 56.
    Schneider, S., Feilen, P.J., Schreckenberger, M., Schwanstecher, M., Schwanstecher, C., Buchholz, H.G., et al.: In vitro and in vivo evaluation of novel glibenclamide derivatives as imaging agents for the non-invasive assessment of the pancreatic islet cell mass in animals and humans. Exp. Clin. Endocr. Diab. 113, 388–395 (2005)CrossRefGoogle Scholar
  57. 57.
    Schneider, S., Ueberberg, S., Korobeynikov, A., Schechinger, W., Schwanstecher, C., Schwanstecher, M., et al.: Synthesis and evaluation of a glibenclamide glucose-conjugate: A potential new lead compound for substituted glibenclamide derivatives as islet imaging agents. Regul Peptides 139, 122–127 (2007)CrossRefGoogle Scholar
  58. 58.
    Schottelius, M., Wester, H.J., Reubi, J.C., Senekowitsch-Schmidtke, R., Schwaiger, M.: Improvement of pharmacokinetics of radioiodinated Tyr(3)-octreotide by conjugation with carbohydrates. Bioconjugate Chem. 13, 1021–1030 (2002)CrossRefGoogle Scholar
  59. 59.
    Zhang, Y.F., Chen, W.G.: Radiolabeled glucagon-like peptide-1 analogues: a new pancreatic beta-cell imaging agent. Nucl. Med. Commun. 33, 223–227 (2012)CrossRefGoogle Scholar
  60. 60.
    Holst, J.J., Deacon, C.F., Vilsboll, T., Krarup, T., Madsbad, S.: Glucagon-like peptide-1, glucose homeostasis and diabetes. Trends Mol. Med. 14, 161–168 (2008)CrossRefGoogle Scholar
  61. 61.
    Deacon, C.F., Johnsen, A.H., Holst, J.J.: Degradation of Glucagon-Like Peptide-1 by Human Plasma in-Vitro Yields an N-Terminally Truncated Peptide That Is a Major Endogenous Metabolite in-Vivo. J. Clin. Endocr. Metab. 80, 952–957 (1995)Google Scholar
  62. 62.
    Wu, Z.H., Liu, S.L., Nair, I., Omori, K., Scott, S., Todorov, I., et al.: Cu-64 Labeled Sarcophagine Exendin-4 for MicroPET Imaging of Glucagon like Peptide-I Receptor Expression. Theranostics 4, 770–777 (2014)CrossRefGoogle Scholar
  63. 63.
    Wu, Z.H., Liu, S.L., Hassink, M., Nair, I., Park, R., Li, L., et al.: Development and Evaluation of F-18-TTCO-Cys(40)-Exendin-4: A PET Probe for Imaging Transplanted Islets. J. Nucl. Med. 54, 244–251 (2013)CrossRefGoogle Scholar
  64. 64.
    Wu, Z., Todorov, I., Li, L., Bading, J.R., Li, Z.B., Nair, I., et al.: In Vivo Imaging of Transplanted Islets with Cu-64-DO3A-VS-Cys(40)-Exendin-4 by Targeting GLP-1 Receptor. Bioconjugate Chem. 22, 1587–1594 (2011)CrossRefGoogle Scholar
  65. 65.
    Brom, M., Woliner-van der Weg, W., Joosten, L., Frielink, C., Bouckenooghe, T., Rijken, P., et al.: Non-invasive quantification of the beta cell mass by SPECT with In-111-labelled exendin. Diabetologia 57, 950–959 (2014)CrossRefGoogle Scholar
  66. 66.
    Brom, M., Joosten, L., Oyen, W.J.G., Gotthardt, M., Boerman, O.C.: Radiolabelled GLP-1 analogues for in vivo targeting of insulinomas. Contrast Media Mol. 7, 160–166 (2012)CrossRefGoogle Scholar
  67. 67.
    Wang, Y., Lim, K., Normandin, M., Zhao, X.J., Cline, G.W., Ding, Y.S.: Synthesis and evaluation of [F-18]exendin (9-39) as a potential biomarker to measure pancreatic beta-cell mass. Nucl. Med. Biol. 39, 167–176 (2012)CrossRefGoogle Scholar
  68. 68.
    Zhang, B., Yang, B., Zhai, C.X., Jiang, B., Wu, Y.L.: The role of exendin-4-conjugated superparamagnetic iron oxide nanoparticles in beta-cell-targeted MRI. Biomaterials 34, 5843–5852 (2013)CrossRefGoogle Scholar
  69. 69.
    Brand, C., Abdel-Atti, D., Zhang, Y.C., Carlin, S., Clardy, S.M., Keliher, E.J., et al.: In Vivo Imaging of GLP-1R with a Targeted Bimodal PET/Fluorescence Imaging Agent. Bioconjugate Chem. 25, 1323–1330 (2014)CrossRefGoogle Scholar
  70. 70.
    Zanzonico, P.: Principles of Nuclear Medicine Imaging: Planar, SPECT, PET, Multi-modality, and Autoradiography Systems. Radiat. Res. 177, 349–364 (2012)CrossRefGoogle Scholar
  71. 71.
    Pittet, M.J., Weissleder, R.: Intravital Imaging. Cell 147, 983–991 (2011)CrossRefGoogle Scholar
  72. 72.
    Malaisse, W.J.: On the track to the beta-cell. Diabetologia 44, 393–406 (2001)CrossRefGoogle Scholar
  73. 73.
    Guillam, M.T., Hummler, E., Schaerer, E., Yeh, J.I., Birnbaum, M.J., Beermann, F., et al.: Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nature Genetics 17, 327–330 (1997)CrossRefGoogle Scholar
  74. 74.
    Srinivas, M., Heerschap, A., Ahrens, E.T., Figdor, C.G., de Vries, I.J.: (19)F MRI for quantitative in vivo cell tracking. Trends in Biotechnology 28, 363–370 (2010)CrossRefGoogle Scholar
  75. 75.
    Lanza, G.M., Yu, X., Winter, P.M., Abendschein, D.R., Karukstis, K.K., Scott, M.J., 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 106, 2842–2877 (2002)CrossRefGoogle Scholar
  76. 76.
    Malaisse, W.J., Zhang, Y., Louchami, K., Sharma, S., Dresselaers, T., Himmelreich, U., et al.: (19)F-heptuloses as tools for the non-invasive imaging of GLUT2-expressing cells. Archives of Biochemistry and Biophysics 517, 138–143 (2012)CrossRefGoogle Scholar
  77. 77.
    Larsen, M.O., Rolin, B., Wilken, M., Carr, R.D., Gotfredsen, C.F.: Measurements of Insulin Secretory Capacity and Glucose Tolerance to Predict Pancreatic β-Cell Mass In Vivo in the Nicotinamide/Streptozotocin Göttingen Minipig, a Model of Moderate Insulin Deficiency and Diabetes. Diabetes 52, 118–123 (2003)CrossRefGoogle Scholar
  78. 78.
    Ran, C., Pantazopoulos, P., Medarova, Z., Moore, A.: Synthesis and testing of beta-cell-specific streptozotocin-derived near-infrared imaging probes. Angewandte Chemie (International ed in English) 46, 8998–9001 (2007)CrossRefGoogle Scholar
  79. 79.
    Wang, Z., Gleichmann, H.: GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice. Diabetes 47, 50–56 (1998)CrossRefGoogle Scholar
  80. 80.
    Orc, L., Thorens, B., Ravazzola, M., Lodish, H.F.: Localization of the pancreatic beta cell glucose transporter to specific plasma membrane domains. Science 245, 295–297 (1989)Google Scholar
  81. 81.
    Duncan, R.H., Davies, G.S.: Alkylation of DNA bases by carcinogenic N-nitrosamine metabolites: A theoretical study. International Journal of Quantum Chemistry 35, 665–677 (1989)CrossRefGoogle Scholar
  82. 82.
    Weihe, E., Schafer, M.K., Erickson, J.D., Eiden, L.E.: Localization of vesicular monoamine transporter isoforms (VMAT1 and VMAT2) to endocrine cells and neurons in rat. Journal of Molecular neuroscience: MN 5, 149–164 (1994)CrossRefGoogle Scholar
  83. 83.
    Anlauf, M., Eissele, R., Schafer, M.K., Eiden, L.E., Arnold, R., Pauser, U., et al.: Expression of the two isoforms of the vesicular monoamine transporter (VMAT1 and VMAT2) in the endocrine pancreas and pancreatic endocrine tumors. The Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society 51, 1027–1040 (2003)CrossRefGoogle Scholar
  84. 84.
    Maffei, A., Liu, Z., Witkowski, P., Moschella, F., Del Pozzo, G., Liu, E., et al.: Identification of tissue-restricted transcripts in human islets. Endocrinology 145, 4513–4521 (2004)CrossRefGoogle Scholar
  85. 85.
    Erickson, J.D., Schafer, M.K., Bonner, T.I., Eiden, L.E., Weihe, E.: Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proceedings of the National Academy of Sciences of the United States of America 93, 5166–5171 (1996)CrossRefGoogle Scholar
  86. 86.
    Simpson, N.R., Souza, F., Witkowski, P., Maffei, A., Raffo, A., Herron, A., et al.: Visualizing pancreatic beta-cell mass with [11C]DTBZ. Nucl. Med. Biol. 33, 855–864 (2006)CrossRefGoogle Scholar
  87. 87.
    Goland, R., Freeby, M., Parsey, R., Saisho, Y., Kumar, D., Simpson, N., et al.: 11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J. Nucl. Med. 50, 382–389 (2009)CrossRefGoogle Scholar
  88. 88.
    Kung, H.F., Lieberman, B.P., Zhuang, Z.P., Oya, S., Kung, M.P., Choi, S.R., et al.: In vivo imaging of vesicular monoamine transporter 2 in pancreas using an (18)F epoxide derivative of tetrabenazine. Nucl. Med. Biol. 35, 825–837 (2008)CrossRefGoogle Scholar
  89. 89.
    Oishi, K., Miyamoto, Y., Saito, H., Murase, K., Ono, K., Sawada, M., et al.: In vivo imaging of transplanted islets labeled with a novel cationic nanoparticle. PLoS One 8, e57046 (2013)CrossRefGoogle Scholar
  90. 90.
    Toso, C., Valle, J.P., Morel, P., Ris, F., Demuylder-Mischler, S., Lepetit-Coiffe, M., et al.: Clinical magnetic resonance imaging of pancreatic islet grafts after iron nanoparticle labeling. Am. J. Transplant. 8, 701–706 (2008)CrossRefGoogle Scholar
  91. 91.
    Jung, M.J., Lee, S.S., Hwang, Y.H., Jung, H.S., Hwang, J.W., Kim, M.J., et al.: MRI of transplanted surface-labeled pancreatic islets with heparinized superparamagnetic iron oxide nanoparticles. Biomaterials 32, 9391–9400 (2011)CrossRefGoogle Scholar
  92. 92.
    Kitamura, N., Nakai, R., Kohda, H., Furuta-Okamoto, K., Iwata, H.: Labeling of islet cells with iron oxide nanoparticles through DNA hybridization for highly sensitive detection by MRI. Bioorganic & Medicinal Chemistry 21, 7175–7181 (2013)CrossRefGoogle Scholar
  93. 93.
    Wang, Y., Blanco-Andujar, C., Zhi, Z.L., So, P.W., Thanh, N.T., Pickup, J.C.: Multilayered nanocoatings incorporating superparamagnetic nanoparticles for tracking of pancreatic islet transplants with magnetic resonance imaging. Chemical Communications 49, 7255–7257 (2013)CrossRefGoogle Scholar
  94. 94.
    Teramura, Y., Kaneda, Y., Iwata, H.: Islet-encapsulation in ultra-thin layer-by-layer membranes of poly(vinyl alcohol) anchored to poly(ethylene glycol)-lipids in the cell membrane. Biomaterials 28, 4818–4825 (2007)CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Min Jun Kim
    • 1
    • 2
  • Yong Hwa Hwang
    • 1
    • 2
  • Dong Yun Lee
    • 1
    • 2
  1. 1.Departments of Bioengineering, College of Engineering, and Institute for Bioengineering and Biopharmaceutical ResearchHanyang UniversitySeoulRepublic of Korea
  2. 2.BK21 PLUS Future Biopharmaceutical Human Resources Training and Research TeamHanyang UniversitySeoulRepublic of Korea

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