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  • Review Article
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Noninvasive imaging of pancreatic β cells

Nature Reviews Endocrinology volume 5, pages 394–400 (2009)Cite this article

Abstract

Noninvasive imaging and quantification of pancreatic, insulin-producing β cells has been considered a high-priority field of investigation for the past decade. In the first review on this issue, attention was already paid to various agents for labeling β cells, including 6-125I-D-glucose, 65Zn, 3H-glibenclamide, 3H-mitiglinide, an 125I-labeled mouse monoclonal antibody against β-cell surface ganglioside(s), D-(U-14C)-glucose and 2-deoxy-2-18F-D-glucose to label glycogen accumulated in β cells in response to sustained hyperglycemia, and, last but not least, an analog of D-mannoheptulose. This Review discusses these methods and further contributions. For instance, emphasis is placed on labeling β cells with 11C-dihydrotetrabenazine, which is the most advanced method at present. Attention is also drawn to the latest approaches for noninvasive imaging and functional characterization of pancreatic β cells. None of these procedures is used in clinical practice yet.

Key Points

  • Noninvasive β-cell imaging could be used to complement information gained during provocative tests that assess the insulin secretory response in individuals with or at high risk of diabetes mellitus

  • One of the main difficulties of noninvasive imaging of β cells resides in the fact that these cells represent only about 1% of the total pancreatic mass

  • Available tools include a D-mannoheptulose analog, alloxan, streptozotocin, hypoglycemic sulfonylureas and glinides, β-cell-specific monoclonal antibodies, L-3,4-dihydroxyphenylalanine, peptidomimetic ligands for somatostatin receptors, dihydratetetrabenazine, optical coherence tomography, and diffusion MRI

  • None of these tools is currently used in clinical practice

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References

  1. Wild, S., Roglic, G., Green, A., Sicree, R. & King, H. Global prevalence of diabetes. Estimates for the year 2000 and projections for 2030. Diabetes Care 27, 1047–1053 (2004).

    Article  Google Scholar 

  2. Robertson, R. P. Estimation of β-cell mass by metabolic tests. Necessary, but how sufficient? Diabetes 56, 2420–2424 (2007).

    Article  CAS  Google Scholar 

  3. Bouwens, L. & Rooman, I. Regulation of pancreatic β-cell mass. Physiol. Rev. 85, 1255–1270 (2005).

    Article  CAS  Google Scholar 

  4. Malaisse, W. J. On the track to the β-cell. Diabetologia 44, 393–406 (2001).

    Article  CAS  Google Scholar 

  5. Malaisse, W. J. Non-invasive imaging of the endocrine pancreas. Int. J. Mol. Med. 15, 243–246 (2005).

    PubMed  Google Scholar 

  6. Paty, B. W., Bonner-Weir, S., Laughlin, M. R., McEwan, A. J. & Shapiro, A. M. Toward development of imaging modalities for islet after transplantation: insights from the National Institutes of Health Workshop on β Cell Imaging. Transplantation 77, 1133–1137 (2004).

    Article  Google Scholar 

  7. Souza, F. et al. Current progress in non-invasive imaging of β cell mass of the endocrine pancreas. Curr. Med. Chem. 13, 2761–2773 (2006).

    Article  CAS  Google Scholar 

  8. Lin, M. et al. Advances in molecular imaging of pancreatic β cells. Front. Biosci. 13, 4558–4575 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Saudek, F., Brogren, C. H. & Manohar, S. Imaging the β-cell mass: why and how. Rev. Diabet. Stud. 5, 6–12 (2008).

    Article  Google Scholar 

  10. Holmberg, D. & Ahlgren, U. Imaging the pancreas: from ex vivo to non-invasive technology. Diabetologia 51, 2148–2154 (2008).

    Article  CAS  Google Scholar 

  11. Medarova, Z. & Moore, A. Non-invasive detection of transplanted pancreatic islets. Diabetes Obes. Metab. 10 (Suppl. 4), 88–97 (2008).

    Article  Google Scholar 

  12. Malaisse, W. J., Ladrière, L. & Malaisse-Lagae, F. Pancreatic fate of 6-deoxy-6-[125I]iodo-D-glucose: in vivo experiments. Endocrine 13, 95–101 (2000).

    Article  CAS  Google Scholar 

  13. Ladrière, L., Malaisse-Lagae, F. & Malaisse, W. J. Pancreatic uptake of 65Zn in control and streptozotocin-injected rats. Med. Sci. Res. 28, 43–44 (2000).

    Google Scholar 

  14. Ladrière, L., Malaisse-Lagae, F. & Malaisse, W. J. Uptake of tritiated glibenclamide by endocrine and exocrine pancreas. Endocrine 13, 133–136 (2000).

    Article  Google Scholar 

  15. Malaisse, W. J. & Malaisse-Lagae, F. Uptake of tritiated mitiglinide by pancreatic pieces and islets. Diabetes Res. 35, 51–59 (2000).

    CAS  Google Scholar 

  16. Ladrière, L., Malaisse-Lagae, F., Alejandro, R. & Malaisse, W. J. Pancreatic fate of a 125I-labelled mouse monoclonal antibody directed against pancreatic β-cell surface ganglioside(s) in control and diabetic rats. Cell Biochem. Funct. 19, 107–115 (2001).

    Article  Google Scholar 

  17. Doherty, M. & Malaisse, W. J. Glycogen accumulation in rat pancreatic islets. In vivo experiments. Endocrine 14, 303–309 (2001).

    Article  CAS  Google Scholar 

  18. Ladrière, L., Leclercq-Meyer, V. & Malaisse, W. J. Assessment of islet β-cell mass in isolated rat pancreases perfused with D-[3H]mannoheptulose. Am. J. Physiol. Endocrinol. Metab. 281, E298–E303 (2001).

    Article  Google Scholar 

  19. Malaisse, W. J., Courtois, P., Kadiata, M. M. & Sener, A. GLUT2-mediated transport of D-mannoheptulose: a tool for imaging of the endocrine pancreas? Diabetes 49 (Suppl. 1), A418 (2000).

    Google Scholar 

  20. Simon, E. J. & Kraicer, P. F. The blockade of insulin secretion by mannoheptulose. Isr. J. Med. Sci. 2, 785–799 (1966).

    CAS  PubMed  Google Scholar 

  21. Simon, E., Frenkel, G. & Kraicer, P. F. Blockade of insulin secretion by mannoheptulose. Isr. J. Med. Sci. 6, 743–752 (1972).

    Google Scholar 

  22. Lev-Ran, A., Laor, J., Vins, M. & Simon, E. Effect of intravenous infusion of D-mannoheptulose on blood glucose and insulin levels in man. J. Endocrinol. 47, 137–138 (1970).

    Article  CAS  Google Scholar 

  23. Paulsen, E. P. Mannoheptulose and insulin inhibition. Ann. NY Acad. Sci. 150, 455–456 (1968).

    Article  CAS  Google Scholar 

  24. Otaga, J. N., Kawano, Y., Bevenue, A. & Casaret, J. L. The ketoheptose content of some tropical fruits. J. Agric. Food Chem. 29, 113–115 (1972).

    Google Scholar 

  25. Viktora, J. K., Johnson, B. F., Penhos, J. C., Rosenberg, C. A. & Wolff, F. W. Effect of ingested mannoheptulose in animals and man. Metabolism 18, 87–102 (1969).

    Article  CAS  Google Scholar 

  26. Johnson, B., Viktora, J. & Wolff, F. The efficacy of oral mannoheptulose in monkey and man [abstract]. Diabetes 18 (Suppl. 1), 360 (1969).

    Google Scholar 

  27. Garber, A. J. in Internal Medicine 3rd edn Ch. 343 (ed Stein, J. H.) 2273–2278 (Little & Brown, Boston, 1990).

    Google Scholar 

  28. Bergh, B. O. The avocado and human nutrition. 1. Some human health aspects of the avocado. In Proc. 2nd World Avocado Congress, 1991 April 21–26; Orange, CA (Eds Lovatt, C. J. et al.) 25–35 (University of California, Riverside, 1992).

    Google Scholar 

  29. Mohamed-Yasseen, Y. Uncommon uses of avocado. Tropical Fruit News 28, 14 (1994).

    Google Scholar 

  30. Sener, A. et al. D-mannoheptulose uptake and its metabolic and secretory effects in human pancreatic islets. Int. J. Mol. Med. 6, 617–620 (2000).

    CAS  PubMed  Google Scholar 

  31. Ferrer, J., Benito, C. & Gomis, R. Pancreatic islet GLUT2 glucose transporter mRNA and protein expression in humans with and without NIDDM. Diabetes 44, 1369–1374 (1995).

    Article  CAS  Google Scholar 

  32. De Vos, A. et al. Human and rat β cells differ in glucose transporter but not in glucokinase gene expression. J. Clin. Invest. 96, 2489–2495 (1995).

    Article  CAS  Google Scholar 

  33. Malaisse, W. J., Doherty, M., Ladrière, L. & Malaisse-Lagae, F. Pancreatic uptake of 2-[14C]alloxan. Int. J. Mol. Med. 7, 311–315 (2001).

    CAS  PubMed  Google Scholar 

  34. Ran, C., Pantazopoulos, P., Medarova, Z. & Moore, A. Synthesis and testing of β-cell-specific streptozotocin-derived near-infrared imaging probes. Angew Chem. Int. Ed. Engl. 46, 8998–9001 (2007).

    Article  CAS  Google Scholar 

  35. Sweet, I. R., Cook, L., Lernmark, A., Greenbaum, C. J. & Krohn, K. A. Non-invasive imaging of β cell mass: a quantitative analysis. Diabetes Technol. Ther. 6, 625–629 (2004).

    Article  Google Scholar 

  36. Wängler, B. et al. Synthesis and evaluation of (S.)-2-(2-[18F]fluoroethoxy)-4- ([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbamoyl]-methyl)-benzoic acid ([18F]repaglinide): a promising radioligand for quantification of pancreatic β-cell mass with positron emission tomography (PET). Nucl. Med. Biol. 31, 639–647 (2004).

    Article  Google Scholar 

  37. Moore, A., Bonner-Weir, S. & Weissleder, R. Noninvasive in vivo measurement of β-cell mass in mouse model of diabetes. Diabetes 50, 2231–2236 (2001).

    Article  CAS  Google Scholar 

  38. Paty, B. W. et al. β Cell 125I-labeled IC2 antibody is a promising method of measuring intra-hepatically-transplanted islet mass in vivo [abstract 45]. Presented at Imaging the Pancreatic β Cell, 2003 April 21–22, Bethesda, MD.

  39. Otonkoski, T. et al. Noninvasive diagnosis of focal hyperinsulinism of infancy with 18F-DOPA positron emission tomography. Diabetes 55, 13–18 (2006).

    Article  CAS  Google Scholar 

  40. Kauhanen, S. et al. 18F-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography as a tool to localize an insulinoma or β-cell hyperplasia in adult patients. J. Clin. Endocrinol. Metab. 92, 1237–1244 (2007).

    Article  CAS  Google Scholar 

  41. Amartey, J. K., Esguerra, C., Al-Jammaz, I., Parhar, R. S. & Al-Otaibi, B. Synthesis and evaluation of radioiodinated substituted β-naphthylalanine as a potential probe for pancreatic β-cells imaging. Appl. Radiat. Isot. 64, 769–777 (2006).

    Article  CAS  Google Scholar 

  42. Evgenov, N. V., Medarova, Z., Dai, G., Bonner-Weir, S. & Moore, A. In vivo imaging of islet transplantation. Nat. Med. 12, 144–148 (2006).

    Article  CAS  Google Scholar 

  43. Evgenov, N. V. et al. In vivo imaging of immune rejection in transplanted pancreatic islets. Diabetes 55, 2419–2428 (2006).

    Article  CAS  Google Scholar 

  44. Evgenov, N. V., Pratt, J., Pantazopoulos. P. & Moore, A. Effects of glucose toxicity and islet purity on in vivo magnetic resonance imaging of transplanted pancreatic islets. Transplantation 85, 1091–1098 (2008).

    Article  Google Scholar 

  45. Koblas, T. et al. Magnetic resonance imaging of intrahepatically transplanted islets using paramagnetic beads. Transplant. Proc. 37, 3493–3495 (2005).

    Article  CAS  Google Scholar 

  46. Toso, C. et al. Clinical magnetic resonance imaging of pancreatic islet grafts after iron nanoparticle labeling. Am. J. Transplant. 8, 701–706 (2008).

    Article  CAS  Google Scholar 

  47. Medarova, Z. et al. Noninvasive magnetic resonance imaging of microvascular changes in type 1 diabetes. Diabetes 56, 2677–2682 (2007).

    Article  CAS  Google Scholar 

  48. Medarova, Z., Bonner-Weir, S., Lipes, M. & Moore, A. Imaging β-cell death with a near-infrared probe. Diabetes 54, 1780–1788 (2005).

    Article  CAS  Google Scholar 

  49. Srinivas, M., Morel, P. A., Ernst, L. A., Laidlaw, D. H. & Ahrens, E. T. 19F-MRI for visualization and quantification of cell migration in a diabetes model. Magn. Reson. Med. 58, 725–734 (2007).

    Article  CAS  Google Scholar 

  50. Medarova, Z., Tsai, S., Evgenov, N., Santamaria, P. & Moore, A. In vivo imaging of a diabetogenic CD8+ T cell response during type 1 diabetes progression. Magn. Reson. Med. 59, 712–720 (2008).

    Article  Google Scholar 

  51. Maffei, A. et al. Identification of tissue-restricted transcripts in human islets. Endocrinology 145, 4513–4521 (2004).

    Article  CAS  Google Scholar 

  52. Simpson, N. R. et al. Visualizing pancreatic β-cell mass with 11C-DTBZ. Nucl. Med. Biol. 33, 855–864 (2006).

    Article  CAS  Google Scholar 

  53. Souza, F. et al. Longitudinal non-invasive PET-based β cell mass estimates in a spontaneous diabetes rat model. J. Clin. Invest. 116, 1506–1513 (2006).

    Article  CAS  Google Scholar 

  54. Kung M.-P. et al. In vivo imaging of β-cell mass in rats using 18F-FP-(+)-DTBZ: a potential PET ligand for studying diabetes mellitus. J. Nucl. Med. 49, 1171–1176 (2008).

    Article  CAS  Google Scholar 

  55. Goland, R. et al. 11C-DTBZ PET imaging of the pancreas in subjects with longstanding type 1 diabetes and healthy controls. J. Nucl. Med. 50, 382–389 (20089).

  56. Harris, P. E. et al. VMAT2 gene expression and function as it applies to imaging β-cell mass. J. Mol. Med. 86, 5–16 (2008).

    Article  CAS  Google Scholar 

  57. Raffo, A. et al. Role of vesicular monoamine transporter type 2 in rodent insulin secretion and glucose metabolism revealed by its specific antagonist tetrabenazine. J. Endocrinol. 198, 1–10 (2008).

    Article  Google Scholar 

  58. Saisho, Y. et al. Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas. J. Mol. Histol. 39, 543–551 (2008).

    Article  CAS  Google Scholar 

  59. Nyqvist, D., Köhler, M., Wahlstedt, H. & Berggren, P.-O. Donor islet endothelial cells participate in formation of functional vessels within pancreatic islet grafts. Diabetes 54, 2287–2293 (2005).

    Article  CAS  Google Scholar 

  60. Speier, S. et al. Noninvasive high-resolution in vivo imaging of cell biology in the anterior chamber of the mouse eye. Nat. Protoc. 3, 1278–1286 (2008).

    Article  CAS  Google Scholar 

  61. Alanentalo, T. et al. Tomographic molecular imaging and 3D quantification within adult mouse organs. Nat. Methods 4, 31–33 (2006).

    Article  Google Scholar 

  62. Le Bihan, D., Urayama, S.-I., Aso, T., Hanakawa, T. & Fukuyama, H. Direct and fast detection of neuronal activation in the human brain with diffusion MRI. Proc. Natl Acad. Sci. USA 103, 8263–8268 (2006).

    Article  CAS  Google Scholar 

  63. Le Bihan, D. See the thinking brain: a story about water [French]. Bull. Mem. Acad. R. Med. Belg. 163, 105–121 (2008).

    CAS  PubMed  Google Scholar 

  64. Miley, H. E., Sheader, E. A., Brown, P. D. & Best, L. Glucose-induced swelling in rat pancreatic β-cells. J. Physiol. 504 (Pt 1), 191–196 (1997).

    Article  CAS  Google Scholar 

  65. Malaisse, W. J. See the thinking brain: a story about water [French]. Bull. Mem. Acad. R. Med. Belg. 163, 121–122 (2008).

    Google Scholar 

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Acknowledgements

The authors wish to thank U. Ahlgren, P. E. Harris and A. Moore for their helpful comments, and E. Hupkens and C. Demesmaeker for secretarial help. The authors' ongoing research on the imaging of GLUT2-positive cells is supported by convention 716627 from Région Wallonne (Belgium).

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Authors and Affiliations

  1. Laboratory of Experimental Hormonology, Université Libre de Bruxelles, Brussels, Belgium

    Willy J. Malaisse, Karim Louchami & Abdullah Sener

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  1. Willy J. Malaisse
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Correspondence to Willy J. Malaisse.

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Malaisse, W., Louchami, K. & Sener, A. Noninvasive imaging of pancreatic β cells. Nat Rev Endocrinol 5, 394–400 (2009). https://doi.org/10.1038/nrendo.2009.103

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