Skip to main content

Advertisement

SpringerLink
Log in

Noninvasive imaging of islet transplantation and rejection

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Immunologic and nonimmunologic events lead to significant graft loss after islet transplantation. Unfortunately, current metabolic testing methods are inadequate to detect many of these changes, leading to a critical need for noninvasive monitoring of islet rejection. However, their small size and distribution after transplantation pose specific problems for direct islet imaging. This article reviews the relative merits of several imaging modalities for the noninvasive monitoring of islet transplantation and rejection.

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

Similar content being viewed by others

References and Recommended Reading

  1. Gaglia JL: The state of islet transplantation. Curr Opin Endocrinol Diabetes 2006, 2:199–204.

    Article  Google Scholar 

  2. McCulloch DK, Raghu PK, Johnston C, et al.: Defects in beta-cell function and insulin sensitivity in normoglycemic streptozocin-treated baboons: a model of preclinical insulin-dependent diabetes. J Clin Endocrinol Metab 1988, 67:785–792.

    Article  PubMed  CAS  Google Scholar 

  3. Pileggi A, Ricordi C, Alessiani M, Inverardi L: Factors influencing Islet of Langerhans graft function and monitoring. Clin Chim Acta 2001, 310:3–16.

    Article  PubMed  CAS  Google Scholar 

  4. Faradji RN, Monroy K, Messinger S, et al.: Simple measures to monitor beta-cell mass and assess islet graft dysfunction. Am J Transplant 2007, 7:303–308.

    Article  PubMed  CAS  Google Scholar 

  5. Matsumoto S, Yamada Y, Okitsu T, et al.: Simple evaluation of engraftment by secretory unit of islet transplant objects for living donor and cadaveric donor fresh or cultured islet transplantation. Transplant Proc 2005, 37:3435–3437.

    Article  PubMed  CAS  Google Scholar 

  6. Secchi A, Pontiroli AE, Traeger J, et al.: A method for early detection of graft failure in pancreas transplantation. Transplantation. 1983, 35:344–348.

    Article  PubMed  CAS  Google Scholar 

  7. Lu Y, Dang H, Middleton B, et al.: Bioluminescent monitoring of islet graft survival after transplantation. Mol Ther 2004, 9:428–435.

    Article  PubMed  CAS  Google Scholar 

  8. Fowler M, Virostko J, Chen Z, et al.: Assessment of pancreatic islet mass after islet transplantation using in vivo bioluminescence imaging. Transplantation 2005, 79:768–776.

    Article  PubMed  Google Scholar 

  9. Virostko J, Chen Z, Fowler M, et al.: Factors influencing quantification of in vivo bioluminescence imaging: application to assessment of pancreatic islet transplants. Mol Imaging 2004, 3:333–342.

    Article  PubMed  Google Scholar 

  10. Chen X, Zhang X, Larson CS, et al.: In vivo bioluminescence imaging of transplanted islets and early detection of graft rejection. Transplantation 2006, 81:1421–1427.

    Article  PubMed  Google Scholar 

  11. 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, 43:80–86.

    Article  PubMed  CAS  Google Scholar 

  12. Roth DJ, Jansen ED, Powers AC, Wang TG: A novel method of monitoring response to islet transplantation: bioluminescent imaging of an NF-kappaB transgenic mouse model. Transplantation 2006, 81:1185–1190.

    Article  PubMed  CAS  Google Scholar 

  13. Branchini BR, Ablamsky DM, Murtiashaw MH, et al.: Thermostable red and green light-producing firefly luciferase mutants for bioluminescent reporter applications. Anal Biochem 2007, 361:253–262.

    Article  PubMed  CAS  Google Scholar 

  14. Cong W, Wang G: Boundary integral method for bioluminescence tomography. J Biomed Opt 2006, 11:020503.

    Article  PubMed  Google Scholar 

  15. Li S, Zhang Q, Jiang H: Two-dimensional bioluminescence tomography: numerical simulations and phantom experiments. Appl Opt 2006, 45:3390–3394.

    Article  PubMed  Google Scholar 

  16. Barnett BP, Kraitchman DL, Lauzon C, et al.: Radiopaque alginate microcapsules for X-ray visualization and immunoprotection of cellular therapeutics. Mol Pharm 2006, 3:531–538.

    Article  PubMed  CAS  Google Scholar 

  17. Bulte J: MR-Guided Cell Therapy: From Nanoprobes to Nanopores. Paper presented at the Imaging the Pancreatic Beta Cell in Health and Disease, Third Workshop. Washington, DC; April 24–25, 2006.

  18. Markmann JF, Rosen M, Siegelman ES, et al.: Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival? Diabetes 2003, 52:1591–1594.

    Article  PubMed  CAS  Google Scholar 

  19. Eckhard M, Lommel D, Hackstein N, et al.: Disseminated periportal fatty degeneration after allogeneic intraportal islet transplantation in a patient with type 1 diabetes mellitus: a case report. Transplant Proc 2004, 36:1111–1116.

    Article  PubMed  CAS  Google Scholar 

  20. Maffi P, Angeli E, Bertuzzi F, et al.: Minimal focal steatosis of liver after islet transplantation in humans: a long-term study. Cell Transplant 2005, 14:727–733.

    PubMed  Google Scholar 

  21. Bhargava R, Senior PA, Ackerman TE, et al.: Prevalence of hepatic steatosis after islet transplantation and its relation to graft function. Diabetes 2004, 53:1311–1317.

    Article  PubMed  CAS  Google Scholar 

  22. Heyn C, Bowen CV, Rutt BK, Foster PJ: Detection threshold of single SPIO-labeled cells with FIESTA. Magn Reson Med 2005, 53:312–320.

    Article  PubMed  Google Scholar 

  23. Evgenov NV, Medarova Z, Dai G, et al.: In vivo imaging of islet transplantation. Nat Med 2006, 12:144–148.

    Article  PubMed  CAS  Google Scholar 

  24. Evgenov NV, Medarova Z, Pratt J, et al.: In vivo imaging of immune rejection in transplanted pancreatic islets. Diabetes 2006, 55:2419–2428.

    Article  PubMed  CAS  Google Scholar 

  25. Jirak D, Kriz J, Herynek V, et al.: MRI of transplanted pancreatic islets. Magn Reson Med 2004, 52:1228–1233.

    Article  PubMed  Google Scholar 

  26. Kriz J, Jirak D, Girman P, et al.: Magnetic resonance imaging of pancreatic islets in tolerance and rejection. Transplantation 2005, 80:1596–1603.

    Article  PubMed  Google Scholar 

  27. Koblas T, Girman P, Berkova Z, et al.: Magnetic resonance imaging of intrahepatically transplanted islets using paramagnetic beads. Transplant Proc 2005, 37:3493–3495.

    Article  PubMed  CAS  Google Scholar 

  28. Tai JH, Foster P, Rosales A, et al.: Imaging islets labeled with magnetic nanoparticles at 1.5 Tesla. Diabetes 2006, 55:2931–2938.

    Article  PubMed  CAS  Google Scholar 

  29. Toso C, Vallee J, Morel P, et al.: Clinical Magnetic Resonance Imaging of Allogeneic Islet Grafts After Iron-Labeling [poster]. Poster presented at the Imaging the Pancreatic Beta Cell in Health and Disease, Third Workshop. Washington, DC; April 24–25, 2006.

  30. Mani V, Briley-Saebo KC, Itskovich VV, et al.: Gradient echo acquisition for superparamagnetic particles with positive contrast (GRASP): sequence characterization in membrane and glass superparamagnetic iron oxide phantoms at 1.5T and 3T. Magn Reson Med 2006, 55:126–135.

    Article  PubMed  CAS  Google Scholar 

  31. Cunningham CH, Arai T, Yang PC, et al.: Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles. Magn Reson Med 2005, 53:999–1005.

    Article  PubMed  CAS  Google Scholar 

  32. Foltz WD, Cunningham CH, Mutsaers AJ, et al.: Positive-contrast imaging in the rabbit hind-limb of transplanted cells bearing endocytosed superparamagnetic beads. J Cardiovasc Magn Reson 2006, 8:817–823.

    Article  PubMed  Google Scholar 

  33. Stuber M, Gilson WD, Schaer M, et al.: Shedding light on the dark spot with IRON—a method that generates positive contrast in the presence of superparamagnetic nanoparticles. Proc Intl Soc Magn Reson Med 2005, 13:2608.

    Google Scholar 

  34. Zurkiya O, Hu X: Off-resonance saturation as a means of generating contrast with superparamagnetic nanoparticles. Magn Reson Med 2006, 56:726–732.

    Article  PubMed  Google Scholar 

  35. Biancone L, Crich SG, Cantaluppi V, et al.: Magnetic resonance imaging of gadolinium-labeled pancreatic islets for experimental transplantation. NMR Biomed 2007, 20:40–48.

    Article  PubMed  Google Scholar 

  36. Zheng Q, Dai H, Merritt ME, et al.: A new class of macrocyclic lanthanide complexes for cell labeling and magnetic resonance imaging applications. J Am Chem Soc 2005, 127:16178–16188.

    Article  PubMed  CAS  Google Scholar 

  37. Sweet IR, Cook DL, Lernmark A, et al.: Non-invasive imaging of beta cell mass: a quantitative analysis. Diabetes Technol Ther 2004, 6:652–659.

    Article  PubMed  Google Scholar 

  38. Schneider S, Feilen PJ, Schreckenberger M, 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 Endocrinol Diabetes 2005, 113:388–395.

    Article  PubMed  CAS  Google Scholar 

  39. Toso C, Zaidi H, Morel P, et al.: Positron-emission tomography imaging of early events after transplantation of islets of Langerhans. Transplantation 2005, 79:353–355.

    Article  PubMed  Google Scholar 

  40. 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, 12:1423–1428.

    Article  PubMed  CAS  Google Scholar 

  41. Moore A, Bonner-Weir S, Weissleder R: Noninvasive in vivo measurement of beta-cell mass in mouse model of diabetes. Diabetes 2001, 50:2231–2236.

    Article  PubMed  CAS  Google Scholar 

  42. Yao VJ, Ozawa MG, Trepel M, et al.: Targeting pancreatic islets with phage display assisted by laser pressure catapult microdissection. Am J Pathol 2005, 166:625–636.

    PubMed  CAS  Google Scholar 

  43. Samli KN, McGuire MJ, Newgard CB, et al.: Peptide-mediated targeting of the islets of Langerhans. Diabetes 2005, 54:2103–2108.

    Article  PubMed  CAS  Google Scholar 

  44. Maffei A, Liu Z, Witkowski P, et al.: Identification of tissue-restricted transcripts in human islets. Endocrinology 2004, 145:4513–4521.

    Article  PubMed  CAS  Google Scholar 

  45. Souza F, Simpson N, Raffo A, et al.: Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model. J Clin Invest 2006, 116:1506–1513.

    Article  PubMed  CAS  Google Scholar 

  46. Simpson NR, Souza F, Witkowski P, et al.: Visualizing pancreatic beta-cell mass with [11C] DTBZ. Nucl Med Biol 2006, 33:855–864.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Harvard Medical School, Joslin Diabetes Center, One Joslin Place, Boston, MA, 02215, USA

    Jason L. Gaglia MD

Authors
  1. Jason L. Gaglia MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jason L. Gaglia MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gaglia, J.L. Noninvasive imaging of islet transplantation and rejection. Curr Diab Rep 7, 309–313 (2007). https://doi.org/10.1007/s11892-007-0050-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-007-0050-2

Keywords

Search

Navigation