Top

Published in:

Open Access 01-05-2012 | Review

Obstacles on the way to the clinical visualisation of beta cells: looking for the Aeneas of molecular imaging to navigate between Scylla and Charybdis

Authors: K. Andralojc, M. Srinivas, M. Brom, L. Joosten, I. J. M. de Vries, D. L. Eizirik, O. C. Boerman, P. Meda, M. Gotthardt

Published in: Diabetologia | Issue 5/2012

Abstract

For more than a decade, researchers have been trying to develop non-invasive imaging techniques for the in vivo measurement of viable pancreatic beta cells. However, in spite of intense research efforts, only one tracer for positron emission tomography (PET) imaging is currently under clinical evaluation. To many diabetologists it may remain unclear why the imaging world struggles to develop an effective method for non-invasive beta cell imaging (BCI), which could be useful for both research and clinical purposes. Here, we provide a concise overview of the obstacles and challenges encountered on the way to such BCI, in both native and transplanted islets. We discuss the major difficulties posed by the anatomical and cell biological features of pancreatic islets, as well as the chemical and physical limits of the main imaging modalities, with special focus on PET, SPECT and MRI. We conclude by indicating new avenues for future research in the field, based on several remarkable recent results.

Weir GC (2004) Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes 53(Suppl 3):S16–S21PubMedCrossRef

Goke B (2010) What are the potential benefits of clinical beta-cell imaging in diabetes mellitus? Curr Pharm Des 16:1547–1549PubMedCrossRef

National Institutes of Health (2009) Imaging the pancreatic beta cell, 4th Workshop, April 6–7. Available from www3.niddk.nih.gov/fund/other/imageislet/index.htm Accessed 1 July 2010

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

Veluthakal R, Harris P (2010) In vivo beta-cell imaging with VMAT 2 ligands—current state-of-the-art and future perspective. Curr Pharm Des 16:1568–1581PubMedCrossRef

Goland R, Freeby M, Parsey R et al (2009) ¹¹C-Dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med 50:382–389PubMedCrossRef

Fagerholm V, Mikkola KK, Ishizu T et al (2010) Assessment of islet specificity of dihydrotetrabenazine radiotracer binding in rat pancreas and human pancreas. J Nucl Med 51:1439–1446PubMedCrossRef

Baum RP, Prasad V, Muller D et al (2010) Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic ¹¹¹In- or ⁶⁸Ga-labeled Affibody molecules. J Nucl Med 51:892–897PubMedCrossRef

Gainkam LO, Huang L, Caveliers V et al (2008) Comparison of the biodistribution and tumor targeting of two ^99mTc-labeled anti-EGFR nanobodies in mice, using pinhole SPECT/micro-CT. J Nucl Med 49:788–795PubMedCrossRef

10.

Wild D, Behe M, Wicki A et al (2006) [Lys⁴⁰(Ahx-DTPA-¹¹¹In)NH₂]exendin-4, a very promising ligand for glucagon-like peptide-1 (GLP-1) receptor targeting. J Nucl Med 47:2025–2033PubMed

11.

Reubi JC, Perren A, Rehmann R et al (2010) Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass. Diabetologia 53:2641–2645PubMedCrossRef

12.

Kauhanen S, Seppanen M, Minn H, Nuutila P (2010) Clinical PET imaging of insulinoma and beta-cell hyperplasia. Curr Pharm Des 16:1550–1560PubMedCrossRef

13.

Sweet IR, Cook DL, Lernmark A et al (2004) Systematic screening of potential beta-cell imaging agents. Biochem Biophys Res Commun 314:976–983PubMedCrossRef

14.

Rubi B, Ljubicic S, Pournourmohammadi S et al (2005) Dopamine D₂-like receptors are expressed in pancreatic beta cells and mediate inhibition of insulin secretion. J Biol Chem 280:36824–36832PubMedCrossRef

15.

de Lonlay P, Simon-Carre A, Ribeiro MJ et al (2006) Congenital hyperinsulinism: pancreatic [¹⁸F]fluoro-l-dihydroxyphenylalanine (DOPA) positron emission tomography and immunohistochemistry study of DOPA decarboxylase and insulin secretion. J Clin Endocrinol Metab 91:933–940PubMedCrossRef

16.

Otonkoski T, Nanto-Salonen K, Seppanen M et al (2006) Noninvasive diagnosis of focal hyperinsulinism of infancy with [¹⁸F]-DOPA positron emission tomography. Diabetes 55:13–18PubMedCrossRef

17.

Anlauf M, Eissele R, Schafer MK et al (2003) Expression of the two isoforms of the vesicular monoamine transporter (VMAT1 and VMAT2) in the endocrine pancreas and pancreatic endocrine tumors. J Histochem Cytochem 51:1027–1040PubMedCrossRef

18.

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

19.

Mei Q, Mundinger TO, Lernmark A, Taborsky GJ Jr (2002) Early, selective, and marked loss of sympathetic nerves from the islets of BioBreeder diabetic rats. Diabetes 51:2997–3002PubMedCrossRef

20.

Eriksson O, Jahan M, Johnstrom P et al (2010) In vivo and in vitro characterization of [¹⁸F]-FE-(+)-DTBZ as a tracer for beta-cell mass. Nucl Med Biol 37:357–363PubMedCrossRef

21.

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

22.

Harris PE, Ferrara C, Barba P, Polito T, Freeby M, Maffei A (2008) VMAT2 gene expression and function as it applies to imaging beta-cell mass. J Mol Med (Berlin, Germany) 86:5–16CrossRef

23.

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

24.

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

25.

Bernardi H, Fosset M, Lazdunski M (1988) Characterization, purification, and affinity labeling of the brain [³H]glibenclamide-binding protein, a putative neuronal ATP-regulated K⁺ channel. Proc Natl Acad Sci U S A 85:9816–9820PubMedCrossRef

26.

Wangler B, Beck C, Shiue CY et al (2004) Synthesis and in vitro evaluation of (S)-2-([¹¹C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-benzoic acid ([¹¹C]methoxy-repaglinide): a potential β-cell imaging agent. Bioorg Med Chem Lett 14:5205–5209PubMedCrossRef

27.

Schmitz A, Shiue CY, Feng Q et al (2004) Synthesis and evaluation of fluorine-18 labeled glyburide analogs as beta-cell imaging agents. Nucl Med Biol 31:483–491PubMedCrossRef

28.

Wangler B, Schneider S, Thews O et al (2004) 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 beta-cell mass with positron emission tomography (PET). Nucl Med Biol 31:639–647PubMedCrossRef

29.

Uttenthal LO, Blazquez E (1990) Characterization of high-affinity receptors for truncated glucagon-like peptide-1 in rat gastric glands. FEBS Lett 262:139–141PubMedCrossRef

30.

Mukai E, Toyoda K, Kimura H et al (2009) GLP-1 receptor antagonist as a potential probe for pancreatic beta-cell imaging. Biochem Biophys Res Commun 389:523–526PubMedCrossRef

31.

Brom M, Baumeister P, Verwijnen S et al (2010) Quantitative determination of the beta cell mass by SPECT imaging with In-111-DTPA-Exendin-3 in rats. Diabetologia 53:S196–S196

32.

Reiner T, Thurber G, Gaglia J et al (2011) Accurate measurement of pancreatic islet beta-cell mass using a second-generation fluorescent exendin-4 analog. Proc Natl Acad Sci U S A 108:12815–12820PubMedCrossRef

33.

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

34.

Ueberberg S, Meier JJ, Waengler C et al (2009) Generation of novel single-chain antibodies by phage-display technology to direct imaging agents highly selective to pancreatic beta- or alpha-cells in vivo. Diabetes 58:2324–2334PubMedCrossRef

35.

Gotthardt M, van Eerd-Vismale J, Oyen WJ et al (2007) Indication for different mechanisms of kidney uptake of radiolabeled peptides. J Nucl Med 48:596–601PubMedCrossRef

36.

Kung HF, Lieberman BP, Zhuang ZP et al (2008) In vivo imaging of vesicular monoamine transporter 2 in pancreas using an ¹⁸F epoxide derivative of tetrabenazine. Nucl Med Biol 35:825–837PubMedCrossRef

37.

Breeman WA, Kwekkeboom DJ, Kooij PP et al (1995) Effect of dose and specific activity on tissue distribution of indium-111-pentetreotide in rats. J Nucl Med 36:623–627PubMed

38.

Brom M, Oyen WJ, Joosten L, Gotthardt M, Boerman OC (2010) ⁶⁸Ga-labelled exendin-3, a new agent for the detection of insulinomas with PET. Eur J Nucl Med Mol Imaging 37:1345–1355PubMedCrossRef

39.

Breeman WA, De Jong M, Visser TJ, Erion JL, Krenning EP (2003) Optimising conditions for radiolabelling of DOTA-peptides with ⁹⁰Y, ¹¹¹In and ¹⁷⁷Lu at high specific activities. Eur J Nucl Med Mol Imaging 30:917–920PubMedCrossRef

40.

Latif ZA, Noel J, Alejandro R (1988) A simple method of staining fresh and cultured islets. Transplantation 45:827–830PubMedCrossRef

41.

Fiedor P, Sitarek E, Tatarkiewicz K, Sabat M, Orlowski T, Rowinski W (1994) In vivo visualization of rat pancreatic islets by intravenous injection of diphenyltiocarbazone (dithizone). Transplant Proc 26:670–671PubMed

42.

Sawada M, Nishikawa M, Adachi T, Midorikawa O, Hiai H (1993) A Paneth cell specific zinc-binding protein in the rat. Purification and immunohistochemical localization. Lab Investig; A Journal of Technical Methods and Pathology 68:338–344

43.

Garnuszek P, Licinska I, Fiedor P, Mazurek AP (1998) The synthesis, radioiodination and preliminary biological study of the new carboxylic derivatives of dithizone. Appl Radiat Isot 49:1563–1571PubMedCrossRef

44.

Sheppard M, Shapiro B, Pimstone B, Kronheim S, Berelowitz M, Gregory M (1979) Metabolic clearance and plasma half-disappearance time of exogenous somatostatin in man. J Clin Endocrinol Metab 48:50–53PubMedCrossRef

45.

Breeman WA, Bakker WH, De Jong M et al (1996) Studies on radiolabeled somatostatin analogues in rats and in patients. Q J Nucl Med 40:209–220PubMed

46.

Bauer W, Briner U, Doepfner W et al (1982) SMS 201-995: a very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sci 31:1133–1140PubMedCrossRef

47.

Marbach P, Briner U, Lemaire M, Schweitzer A, Terasaki T (1993) From somatostatin to Sandostatin: pharmacodynamics and pharmacokinetics. Digestion 54(Suppl 1):9–13PubMedCrossRef

48.

Krenning EP, Kooij PP, Pauwels S et al (1996) Somatostatin receptor: scintigraphy and radionuclide therapy. Digestion 57(Suppl 1):57–61PubMedCrossRef

49.

Krenning EP, Kwekkeboom DJ, Bakker WH et al (1993) Somatostatin receptor scintigraphy with [¹¹¹In-DTPA-d-Phe¹]- and [¹²³I-Tyr³]-octreotide: the Rotterdam experience with more than 1,000 patients. Eur J Nucl Med 20:716–731PubMedCrossRef

50.

Kim JG, Baggio LL, Bridon DP et al (2003) Development and characterization of a glucagon-like peptide 1-albumin conjugate: the ability to activate the glucagon-like peptide 1 receptor in vivo. Diabetes 52:751–759PubMedCrossRef

51.

Shapiro AM, Lakey JR, Ryan EA et al (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343:230–238PubMedCrossRef

52.

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

53.

Lu Y, Dang H, Middleton B et al (2006) Noninvasive imaging of islet grafts using positron-emission tomography. Proc Natl Acad Sci U S A 103:11294–11299PubMedCrossRef

54.

Kim SJ, Doudet DJ, Studenov AR et al (2006) Quantitative micro positron emission tomography (PET) imaging for the in vivo determination of pancreatic islet graft survival. Nat Med 12:1423–1428PubMedCrossRef

55.

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

56.

Smirnov P, Poirier-Quinot M, Wilhelm C et al (2008) In vivo single cell detection of tumor-infiltrating lymphocytes with a clinical 1.5 Tesla MRI system. Magn Reson Med 60:1292–1297PubMedCrossRef

57.

Lamprianou S, Immonen R, Nabuurs C et al (2011) High-resolution magnetic resonance imaging quantitatively detects individual pancreatic islets. Diabetes 60:2853–2860PubMedCrossRef

58.

Sakata N, Hayes P, Tan A et al (2009) MRI assessment of ischemic liver after intraportal islet transplantation. Transplantation 87:825–830PubMedCrossRef

59.

Barrett T, Brechbiel M, Bernardo M, Choyke PL (2007) MRI of tumor angiogenesis. J Magn Reson Imaging 26:235–249PubMedCrossRef

60.

Pollock JM, Tan H, Kraft RA, Whitlow CT, Burdette JH, Maldjian JA (2009) Arterial spin-labeled MR perfusion imaging: clinical applications. Magn Reson Imaging Clin N Am 17:315–338PubMedCrossRef

61.

Hirshberg B, Qiu M, Cali AM et al (2009) Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging. Diabetologia 52:1561–1565PubMedCrossRef

62.

Turvey SE, Swart E, Denis MC et al (2005) Noninvasive imaging of pancreatic inflammation and its reversal in type 1 diabetes. J Clin Investig 115:2454–2461PubMedCrossRef

63.

Chan N, Obenaus A, Tan A et al (2009) Monitoring neovascularization of intraportal islet grafts by dynamic contrast enhanced magnetic resonance imaging. Islets 1:249–255CrossRef

64.

Gimi B, Leoni L, Oberholzer J et al (2006) Functional MR microimaging of pancreatic beta-cell activation. Cell Transplant 15:195–203PubMedCrossRef

65.

Gaglia JL, Guimaraes AR, Harisinghani M et al (2011) Noninvasive imaging of pancreatic islet inflammation in type 1A diabetes patients. J Clin Investig 121:442–445PubMedCrossRef

66.

Kalliokoski T, Simell O, Haaparanta M et al (2005) An autoradiographic study of [¹⁸F]FDG uptake to islets of Langerhans in NOD mouse. Diabetes Res Clin Pract 70:217–224PubMedCrossRef

67.

Kalliokoski T, Nuutila P, Virtanen KA et al (2008) Pancreatic glucose uptake in vivo in men with newly diagnosed type 1 diabetes. J Clin Endocrinol Metab 93:1909–1914PubMedCrossRef

68.

Huang H, Xie Q, Kang M et al (2009) Labeling transplanted mice islet with polyvinylpyrrolidone coated superparamagnetic iron oxide nanoparticles for in vivo detection by magnetic resonance imaging. Nanotechnology 20:365101PubMedCrossRef

69.

Zhang S, He H, Lu W, Xu Q, Zhou B, Tang X (2009) Tracking intrahepatically transplanted islets labeled with Feridex-polyethyleneimine complex using a clinical 3.0-T magnetic resonance imaging scanner. Pancreas 38:293–302PubMedCrossRef

70.

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

71.

Jiao Y, Peng ZH, Zhang JY, Qin J, Zhong CP (2008) Liposome-mediated transfer can improve the efficacy of islet labeling with superparamagnetic iron oxide. Transplant Proc 40:3615–3618PubMedCrossRef

72.

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

73.

Berkova Z, Kriz J, Girman P et al (2005) Vitality of pancreatic islets labeled for magnetic resonance imaging with iron particles. Transplant Proc 37:3496–3498PubMedCrossRef

74.

Kim HS, Choi Y, Song IC, Moon WK (2009) Magnetic resonance imaging and biological properties of pancreatic islets labeled with iron oxide nanoparticles. NMR Biomed 22:852–856PubMedCrossRef

75.

Gauden AJ, Phal PM, Drummond KJ (2010) MRI safety: nephrogenic systemic fibrosis and other risks. J Clin Neurosci 17:1097–1104PubMedCrossRef

76.

Zimmermann H, Zimmermann D, Reuss R et al (2005) Towards a medically approved technology for alginate-based microcapsules allowing long-term immunoisolated transplantation. J Mater Sci 16:491–501

77.

Murua A, Portero A, Orive G, Hernandez RM, de Castro M, Pedraz JL (2008) Cell microencapsulation technology: towards clinical application. J Control Release 132:76–83PubMedCrossRef

78.

Lin H, Cai X (2006) The advance and limitation of microencapsulated grafts transplantation. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi (article in Chinese) 23:678–683

79.

de Vos P, Spasojevic M, Faas MM (2010) Treatment of diabetes with encapsulated islets. Adv Exp Med Biol 670:38–53PubMedCrossRef

80.

de Vries IJ, Lesterhuis WJ, Barentsz JO et al (2005) Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 23:1407–1413PubMedCrossRef

81.

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

82.

Marzola P, Longoni B, Szilagyi E et al (2009) In vivo visualization of transplanted pancreatic islets by MRI: comparison between in vivo, histological and electron microscopy findings. Contrast Media Mol Imaging 4:135–142PubMedCrossRef

83.

Medarova Z, Vallabhajosyula P, Tena A et al (2009) In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates. Transplantation 87:1659–1666PubMedCrossRef

84.

Crowe LA, Ris F, Nielles-Vallespin S et al (2011) A novel method for quantitative monitoring of transplanted islets of Langerhans by positive contrast magnetic resonance imaging. Am J Transplant 11:1158–1168PubMedCrossRef

85.

Srinivas M, Turner MS, Janjic JM, Morel PA, Laidlaw DH, Ahrens ET (2009) In vivo cytometry of antigen-specific T cells using ¹⁹F MRI. Magn Reson Med 62:747–753PubMedCrossRef

86.

Srinivas M, Heerschap A, Ahrens ET, Figdor CG, de Vries IJ (2010) ¹⁹F MRI for quantitative in vivo cell tracking. Trends Biotechnol 28:363–370PubMedCrossRef

87.

Srinivas M, Morel PA, Ernst LA, Laidlaw DH, Ahrens ET (2007) Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model. Magn Reson Med 58:725–734PubMedCrossRef

88.

Bonetto F, Srinivas M, Heerschap A et al (2011) A novel ¹⁹F agent for detection and quantification of human dendritic cells using magnetic resonance imaging. Int J Cancer 129:365–373PubMedCrossRef

89.

Srinivas M, Cruz LJ, Bonetto F, Heerschap A, Figdor CG, de Vries IJ (2010) Customizable, multi-functional fluorocarbon nanoparticles for quantitative in vivo imaging using ¹⁹F MRI and optical imaging. Biomaterials 31:7070–7077PubMedCrossRef

90.

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

91.

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

92.

Hyon SH, Ceballos MC, Barbich M et al (2004) Effect of the embolization of completely unpurified islets on portal vein pressure and hepatic biochemistry in clinical practice. Cell Transplant 13:61–65PubMed

93.

De Leon-Rodriguez LM, Lubag AJ, Malloy CR, Martinez GV, Gillies RJ, Sherry AD (2009) Responsive MRI agents for sensing metabolism in vivo. Acc Chem Res 42:948–957PubMedCrossRef

94.

Hyodo F, Soule BP, Matsumoto K et al (2008) Assessment of tissue redox status using metabolic responsive contrast agents and magnetic resonance imaging. J Pharm Pharmacol 60:1049–1060PubMedCrossRef

95.

Woods M, Woessner DE, Sherry AD (2006) Paramagnetic lanthanide complexes as PARACEST agents for medical imaging. Chem Soc Rev 35:500–511PubMedCrossRef

96.

Villiger M, Goulley J, Friedrich M et al (2009) In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy. Diabetologia 52:1599–1607PubMedCrossRef

97.

Virostko J, Henske J, Vinet L et al (2011) Multimodal image co-registration and inducible selective cell ablation to evaluate imaging ligands. Proc Natl Acad Sci USA 108:20719–20724PubMedCrossRef

98.

Bouckenooghe T, Flamez D, Ortis F, Goldman S, Eizirik DL (2010) Identification of new pancreatic beta cell targets for in vivo imaging by a systems biology approach. Curr Pharm Des 16:1609–1618PubMedCrossRef

99.

Flamez D, Roland I, Berton A et al (2010) A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)γa as a pancreatic beta cell-specific biomarker. Diabetologia 53:1372–1383PubMedCrossRef

100.

Ortis F, Naamane N, Flamez D et al (2010) Cytokines interleukin-1β and tumor necrosis factor-α regulate different transcriptional and alternative splicing networks in primary β-cells. Diabetes 59:358–374PubMedCrossRef

101.

Montet X, Funovics M, Montet-Abou K, Weissleder R, Josephson L (2006) Multivalent effects of RGD peptides obtained by nanoparticle display. J Med Chem 49:6087–6093PubMedCrossRef

102.

Meda P (2012) Symposium on β-cell imaging at the 2011 EANM meeting. Imaging Med (in press)

103.

De Groeve K, Deschacht N, De Koninck C et al (2010) Nanobodies as tools for in vivo imaging of specific immune cell types. J Nucl Med 51:782–789PubMedCrossRef

104.

Leoni L, Serai SD, Haque ME, Magin RL, Roman BB (2010) Functional MRI characterization of isolated human islet activation. NMR Biomed 23:1158–1165PubMedCrossRef

105.

Antkowiak PF, Tersey SA, Carter JD et al (2009) Noninvasive assessment of pancreatic beta-cell function in vivo with manganese-enhanced magnetic resonance imaging. Am J Physiol 296:E573–E578

Title: Obstacles on the way to the clinical visualisation of beta cells: looking for the Aeneas of molecular imaging to navigate between Scylla and Charybdis
Authors: K. Andralojc
M. Srinivas
M. Brom
L. Joosten
I. J. M. de Vries
D. L. Eizirik
O. C. Boerman
P. Meda
M. Gotthardt
Publication date: 01-05-2012
Publisher: Springer-Verlag
Published in: Diabetologia / Issue 5/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-012-2491-7

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2012

Pancreatic diabetes manifests when beta cell area declines by approximately 65% in humans

Exercise in type 2 diabetes: to resist or to endure?

Time dynamics of autoantibodies are coupled to phenotypes and add to the heterogeneity of autoimmune diabetes in adults: the HUNT study, Norway

Descriptive epidemiology of type 1 diabetes—is it still in?

Both resistance- and endurance-type exercise reduce the prevalence of hyperglycaemia in individuals with impaired glucose tolerance and in insulin-treated and non-insulin-treated type 2 diabetic patients

Serum 25-hydroxyvitamin D level during early pregnancy and type 1 diabetes risk in the offspring

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials