Skip to main content

Advertisement

SpringerLink
Log in

Noninvasive Imaging Techniques in Islet Transplantation

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Since the Edmonton trials, insulin independence can reproducibly be achieved after islet transplantation. However, a majority of patients resume insulin treatment in the first 5 years after transplantation. Several mechanisms have been proposed but are difficult to pinpoint in one particular patient. Current tools for the metabolic monitoring of islet grafts indicate islet dysfunction when it is too late to take action. Noninvasive imaging of transplanted islets could be used to study β-cell mass and β-cell function just after infusion, during vascularization or autoimmune and alloimmune attacks. This review will focus on the most recent advances in various imaging techniques (bioluminescence imaging, fluorescence optical imaging, MRI, and positron emission tomography). Emphasis will be placed on pertinent approaches for translation to human practice.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343(4):230–8.

    Article  PubMed  CAS  Google Scholar 

  2. Barshes NR, Wyllie S, Goss JA. Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts. J Leukoc Biol. 2005;77(5):587–97.

    Article  PubMed  CAS  Google Scholar 

  3. Ryan EA, Paty BW, Senior PA, et al. Five-year follow-up after clinical islet transplantation. Diabetes. 2005;54(7):2060–9.

    Article  PubMed  CAS  Google Scholar 

  4. Roelen DL, Huurman VA, Hilbrands R, et al. Relevance of cytotoxic alloreactivity under different immunosuppressive regimens in clinical islet cell transplantation. Clin Exp Immunol. 2009;156(1):141–8.

    Article  PubMed  CAS  Google Scholar 

  5. Huurman VA, Velthuis JH, Hilbrands R, et al. Allograft-specific cytokine profiles associate with clinical outcome after islet cell transplantation. Am J Transplant. 2009;9(2):382–8.

    Article  PubMed  CAS  Google Scholar 

  6. Huurman VA, Hilbrands R, Pinkse GG, et al. Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation. PLoS One. 2008;3(6):e2435.

    Article  PubMed  Google Scholar 

  7. Bellin MD, Sutherland DE, Beilman GJ, et al. Similar islet function in islet allotransplant and autotransplant recipients, despite lower islet mass in autotransplants. Transplantation. 2011;91(3):367–72.

    Article  PubMed  Google Scholar 

  8. Niclauss N, Bosco D, Morel P, et al. Rapamycin impairs proliferation of transplanted islet beta cells. Transplantation. 2011;91(7):714–22.

    PubMed  CAS  Google Scholar 

  9. Berney T, Toso C. Monitoring of the islet graft. Diabetes Metab. 2006;32(5 Pt 2):503–12.

    Article  PubMed  CAS  Google Scholar 

  10. Ferrari-Lacraz S, Berney T, Morel P, et al. Low risk of anti-human leukocyte antigen antibody sensitization after combined kidney and islet transplantation. Transplantation. 2008;86(2):357–9.

    Article  PubMed  CAS  Google Scholar 

  11. Bosi E, Braghi S, Maffi P, et al. Autoantibody response to islet transplantation in type 1 diabetes. Diabetes. 2001;50(11):2464–71.

    Article  PubMed  CAS  Google Scholar 

  12. Kessler L, Parissiadis A, Bayle F, et al. Evidence for humoral rejection of a pancreatic islet graft and rescue with rituximab and IV immunoglobulin therapy. Am J Transplant. 2009;9(8):1961–6.

    Article  PubMed  CAS  Google Scholar 

  13. Lacotte S, Berney T, Shapiro AJ, Toso C. Immune monitoring of pancreatic islet graft: towards a better understanding, detection and treatment of harmful events. Expert Opin Biol Ther. 2011;11(1):55–66.

    Article  PubMed  Google Scholar 

  14. Toso C, Isse K, Demetris AJ, et al. Histologic graft assessment after clinical islet transplantation. Transplantation. 2009;88(11):1286–93.

    Article  PubMed  Google Scholar 

  15. Gaglia JL. Noninvasive imaging of islet transplantation and rejection. Curr Diab Rep. 2007;7(4):309–13.

    Article  PubMed  Google Scholar 

  16. Fowler M, Virostko J, Chen Z, et al. Assessment of pancreatic islet mass after islet transplantation using in vivo bioluminescence imaging. Transplantation. 2005;79(7):768–76.

    Article  PubMed  Google Scholar 

  17. • Chen X, X Zhang, C Larson, et al. Prolonging islet allograft survival using in vivo bioluminescence imaging to guide timing of antilymphocyte serum treatment of rejection. Transplantation. 2008;85(9):1246–52. This paper demonstrates that allogeneic islet grafts can be salvaged by ALS injection when rejection diagnosis was based on bioluminescence signal before rise in glycemia.

    Article  PubMed  Google Scholar 

  18. Park SY, Wang X, Chen Z, et al. Optical imaging of pancreatic beta cells in living mice expressing a mouse insulin I promoter-firefly luciferase transgene. Genesis. 2005;43(2):80–6.

    Article  PubMed  CAS  Google Scholar 

  19. Virostko J, Radhika A, Poffenberger G, et al. Bioluminescence imaging in mouse models quantifies beta cell mass in the pancreas and after islet transplantation. Mol Imaging Biol. 2010;12(1):42–53.

    Article  PubMed  Google Scholar 

  20. Evgenov NV, Medarova Z, Dai G, et al. In vivo imaging of islet transplantation. Nat Med. 2006;12(1):144–8.

    Article  PubMed  CAS  Google Scholar 

  21. Speier S, Nyqvist D, Cabrera O, et al. Noninvasive in vivo imaging of pancreatic islet cell biology. Nat Med. 2008;14(5):574–8.

    Article  PubMed  CAS  Google Scholar 

  22. Perez VL, A Caicedo, DM Berman, et al. The anterior chamber of the eye as a clinical transplantation site for the treatment of diabetes: a study in a baboon model of diabetes. Diabetologia. 54(5):1121–26.

  23. Jirak D, Kriz J, Herynek V, et al. MRI of transplanted pancreatic islets. Magn Reson Med. 2004;52(6):1228–33.

    Article  PubMed  Google Scholar 

  24. Ris F, Lepetit-Coiffe M, Meda P, et al. Assessment of human islet labeling with clinical grade iron nanoparticles prior to transplantation for graft monitoring by MRI. Cell Transplant. 2010;19(12):1573–85.

    Article  PubMed  Google Scholar 

  25. Malosio ML, Esposito A, Poletti A. Improving the procedure for detection of intrahepatic transplanted islets by magnetic resonance imaging. Am J Transplant. 2009;9(10):2372–82.

    Article  PubMed  CAS  Google Scholar 

  26. Evgenov NV, Medarova Z, Pratt J, et al. In vivo imaging of immune rejection in transplanted pancreatic islets. Diabetes. 2006;55(9):2419–28.

    Article  PubMed  CAS  Google Scholar 

  27. Kriz J, Jirak D, Girman P, et al. Magnetic resonance imaging of pancreatic islets in tolerance and rejection. Transplantation. 2005;80(11):1596–603.

    Article  PubMed  Google Scholar 

  28. Jiao Y, Peng ZH, Zhang JY, et al. Liposome-mediated transfer can improve the efficacy of islet labeling with superparamagnetic iron oxide. Transplant Proc. 2008;40(10):3615–8.

    Article  PubMed  CAS  Google Scholar 

  29. Zhang S, He H, Lu W, et al. Tracking intrahepatically transplanted islets labeled with Feridex-polyethyleneimine complex using a clinical 3.0-T magnetic resonance imaging scanner. Pancreas. 2009;38(3):293–302.

    Article  PubMed  CAS  Google Scholar 

  30. Evgenov NV, Pratt J, Pantazopoulos P, Moore A. Effects of glucose toxicity and islet purity on in vivo magnetic resonance imaging of transplanted pancreatic islets. Transplantation. 2008;85(8):1091–8.

    Article  PubMed  Google Scholar 

  31. • Saudek F, D Jirak, P Girman, et al. Magnetic resonance imaging of pancreatic islets transplanted into the liver in humans. Transplantation. 2010;90(12):1602–06. This is a pilot study of SPIO-labeled islet imaging in humans. Islets could be observed in the majority of subjects. The signal strongly decreased 1 week after transplantation and remained stable up to 24 weeks, but no correlation was observed between the MRI signal and the number of transplanted islets.

    Article  PubMed  Google Scholar 

  32. Medarova Z, Vallabhajosyula P, Tena A, et al. In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates. Transplantation. 2009;87(11):1659–66.

    Article  PubMed  Google Scholar 

  33. • Crowe LA, F Ris, S Nielles-Vallespin, et al. A novel method for quantitative monitoring of transplanted islets of langerhans by positive contrast magnetic resonance imaging. Am J Transplant. 2011;11(6):1158–68. This discusses a new semiautomated quantification method of MRI signal coming from SPIO-labeled islets that can be translated in humans.

    Article  PubMed  CAS  Google Scholar 

  34. Toso C, Vallee JP, Morel P, et al. Clinical magnetic resonance imaging of pancreatic islet grafts after iron nanoparticle labeling. Am J Transplant. 2008;8(3):701–6.

    Article  PubMed  CAS  Google Scholar 

  35. Juang JH, Wang JJ, Shen CR, et al. Magnetic resonance imaging of transplanted mouse islets labeled with chitosan-coated superparamagnetic iron oxide nanoparticles. Transplant Proc. 2010;42(6):2104–8.

    Article  PubMed  CAS  Google Scholar 

  36. • Lee N, H Kim, SH Choi, et al. Magnetosome-like ferrimagnetic iron oxide nanocubes for highly sensitive MRI of single cells and transplanted pancreatic islets. Proc Natl Acad Sci USA. 2011;108(7):2662–67. This discusses a new iron particle for pretransplantation islet labeling giving a stronger hyposignal on T2-weighted sequences than Feridex.

    Article  PubMed  CAS  Google Scholar 

  37. Biancone L, Crich SG, Cantaluppi V, et al. Magnetic resonance imaging of gadolinium-labeled pancreatic islets for experimental transplantation. NMR Biomed. 2007;20(1):40–8.

    Article  PubMed  Google Scholar 

  38. Barnett BP, Arepally A, Karmarkar PV, et al. Magnetic resonance-guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells. Nat Med. 2007;13(8):986–91.

    Article  PubMed  CAS  Google Scholar 

  39. • Barnett BP, J Ruiz-Cabello, P Hota, et al. Fluorocapsules for improved function, immunoprotection, and visualization of cellular therapeutics with MR, US, and CT imaging. Radiology. 2011;258(1):182–91. Describes islet encapsulation with the addition of perfluorocarbon inside the capsule, acting as a multimodal contrast agent, detected by MRI, ultrasonography, and CT imaging.

    Article  PubMed  Google Scholar 

  40. Antkowiak PF, Tersey SA, Carter JD, et al. Noninvasive assessment of pancreatic beta-cell function in vivo with manganese-enhanced magnetic resonance imaging. Am J Physiol Endocrinol Metab. 2009;296(3):E573–8.

    Article  PubMed  CAS  Google Scholar 

  41. Hathout E, Sowers L, Wang R, et al. In vivo magnetic resonance imaging of vascularization in islet transplantation. Transpl Int. 2007;20(12):1059–65.

    Article  PubMed  Google Scholar 

  42. Chan NK, Obenaus A, Tan A, et al. Monitoring neovascularization of intraportal islet grafts by dynamic contrast enhanced magnetic resonance imaging. Islets. 2009;1(3):249–55.

    Article  Google Scholar 

  43. Sakata N, Obenaus A, Chan NK, et al. Correlation between angiogenesis and islet graft function in diabetic mice: magnetic resonance imaging assessment. J Hepatobiliary Pancreat Sci. 2010;17(5):692–700.

    Article  PubMed  Google Scholar 

  44. Denis MC, Mahmood U, Benoist C, et al. Imaging inflammation of the pancreatic islets in type 1 diabetes. Proc Natl Acad Sci USA. 2004;101(34):12634–9.

    Article  PubMed  CAS  Google Scholar 

  45. Toso C, Zaidi H, Morel P, et al. Positron-emission tomography imaging of early events after transplantation of islets of Langerhans. Transplantation. 2005;79(3):353–5.

    Article  PubMed  Google Scholar 

  46. • Eriksson O, T Eich, A Sundin, et al. Positron emission tomography in clinical islet transplantation. Am J Transplant. 2009;9(12):2816–24. Using [ 18 F]FDG-prelabeled islets, authors observed that 25% of the injected radioactivity was lost just after infusion, suggesting loss of islets during procedure. This technique can also study the islet distribution in the human liver.

    Article  PubMed  CAS  Google Scholar 

  47. Lu Y, Dang H, Middleton B, et al. Noninvasive imaging of islet grafts using positron-emission tomography. Proc Natl Acad Sci USA. 2006;103(30):11294–9.

    Article  PubMed  CAS  Google Scholar 

  48. Kim SJ, Doudet DJ, Studenov AR, et al. Quantitative micro positron emission tomography (PET) imaging for the in vivo determination of pancreatic islet graft survival. Nat Med. 2006;12(12):1423–8.

    Article  PubMed  CAS  Google Scholar 

  49. Lu Y, Dang H, Middleton B, et al. Long-term monitoring of transplanted islets using positron emission tomography. Mol Ther. 2006;14(6):851–6.

    Article  PubMed  CAS  Google Scholar 

  50. •• Wu Z, F Kandeel. Radionuclide probes for molecular imaging of pancreatic beta-cells. Adv Drug Deliv Rev. 2010;62(11):1125–38. This is a comprehensive review of potential nuclear probes for PET β-cell imaging.

    Article  PubMed  CAS  Google Scholar 

  51. Wild D, Wicki A, Mansi R, et al. Exendin-4-based radiopharmaceuticals for glucagonlike peptide-1 receptor PET/CT and SPECT/CT. J Nucl Med. 2010;51(7):1059–67.

    Article  PubMed  CAS  Google Scholar 

  52. • Christ E, D Wild, F Forrer, et al. Glucagon-like peptide-1 receptor imaging for localization of insulinomas. J Clin Endocrinol Metab. 2009;94(11):4398–405. PET GLP-1 receptor imaging with [111In]DOTA-exendin-4 probe is effective to diagnose pancreas insulinoma and could be a potential technique for transplanted islet imaging.

    Article  PubMed  CAS  Google Scholar 

  53. Pattou F, Kerr-Conte J, Wild D. GLP-1-receptor scanning for imaging of human beta cells transplanted in muscle. N Engl J Med. 2010;363(13):1289–90.

    Article  PubMed  Google Scholar 

  54. Ris F, Toso C, Morel P, et al. Imaging of islets grafts. Curr Opin Organ Transplant. 2007;12:659–63.

    Article  Google Scholar 

  55. Sweet IR, Cook DL, Lernmark A, et al. Non-invasive imaging of beta cell mass: a quantitative analysis. Diabetes Technol Ther. 2004;6(5):652–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

C. Toso was supported by the Swiss National Science Foundation (SCORE grant 3232230–126233). T. Berney was supported by the Swiss National Science Foundation (grant 320030-127583/1) and Insuleman.

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Cell Isolation and Transplant Center, University of Geneva, Level R, 1 rue Michel Servet, CH-1211, GENEVA 4, Switzerland

    Sophie Borot

  2. School of Medicine, University of Franche-Comté, Besançon, France

    Sophie Borot

  3. Department of Radiology, University of Geneva, School of Medicine and Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, CH-1211, GENEVA 14, Switzerland

    Lindsey A. Crowe & Jean-Paul Vallée

  4. Department of Visceral Surgery, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, CH-1211, GENEVA 14, Switzerland

    Christian Toso & Thierry Berney

Authors
  1. Sophie Borot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lindsey A. Crowe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christian Toso
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jean-Paul Vallée
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thierry Berney
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Sophie Borot or Thierry Berney.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Borot, S., Crowe, L.A., Toso, C. et al. Noninvasive Imaging Techniques in Islet Transplantation. Curr Diab Rep 11, 375–383 (2011). https://doi.org/10.1007/s11892-011-0215-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-011-0215-x

Keywords

Search

Navigation