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Approaches for Imaging Pancreatic Islets: Recent Advances and Future Prospects

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Islets of Langerhans, 2. ed.

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Abstract

Many questions about the natural history of both type 1 and type 2 diabetes remain unanswered, mostly because our present knowledge is derived from either in vitro studies or quite indirect in vivo measurements. Methods to noninvasively and repeatedly evaluate the mass and function of β-cells in vivo, two parameters that are central to the study of diabetes, are expected to change our understanding of this disease. However, and in spite of remarkable progress in many imaging techniques, no method yet fulfills the minimal requirements required for such an imaging, because of a combination of anatomical, biological, and technological problems. Here, we briefly review the major optical methods, which have been applied in imaging of the pancreatic β-cells, as well as the nonoptical methods, which may become relevant for the clinical assessment of islets, with particular attention to the individual advantages and limits of each approach.

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References

  • Antkowiak PF, Tersey SA, Carter JD, Vandsburger MH, Nadler JL, Epstein FH, Mirmira RG (2009) Noninvasive assessment of pancreatic beta-cell function in vivo with manganese-enhanced magnetic resonance imaging. Am J Physiol Endocrinol Metab 296:E573–E578

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Antkowiak PF, Vandsburger MH, Epstein FH (2012) Quantitative pancreatic β cell MRI using manganese-enhanced Look-Locker imaging and two-site water exchange analysis. Magn Reson Med 67:1730–1739

    Article  PubMed  Google Scholar 

  • Antkowiak PF, Stevens BK, Nunemaker CS et al (2013) Manganese-enhanced magnetic resonance imaging detects declining pancreatic beta-cell mass in a cyclophosphamide-accelerated mouse model of type 1 diabetes. Diabetes 62:44–48

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Barnett BP, Ruiz-Cabello J, Hota P et al (2011) Fluorocapsules for improved function, immunoprotection, and visualization of cellular therapeutics with MR, US, and CT imaging. Radiology 258:182–191

    Article  PubMed Central  PubMed  Google Scholar 

  • Barone B, Dantas JR, Almeida MH et al (2011) Pancreatic autoantibodies, HLA DR and PTPN22 polymorphisms in first degree relatives of patients with type 1 diabetes and multiethnic background. Exp Clin Endocrinol Diabetes 119:618–620

    Article  PubMed  CAS  Google Scholar 

  • Behm CZ, Lindner JR (2006) Cellular and molecular imaging with targeted contrast ultrasound. Ultrasound Q 22:67–72

    PubMed  Google Scholar 

  • Berclaz C, Goulley J, Villiger M et al (2012) Diabetes imaging-quantitative assessment of islets of Langerhans distribution in murine pancreas using extended-focus optical coherence microscopy. Biomed Opt Express 3:1365–1380

    Article  PubMed Central  PubMed  Google Scholar 

  • Biancone L, Crich SG, Cantaluppi V, Romanazzi GM, Russo S, Scalabrino E, Esposito G, Figliolini F, Beltramo S, Perin PC, Segoloni GP, Aime S, Camussi G (2007) Magnetic resonance imaging of gadolinium-labeled pancreatic islets for experimental transplantation. NMR Biomed 20:40–48

    Article  PubMed  Google Scholar 

  • Botsikas D, Terraz S, Vinet L et al (2012) Pancreatic magnetic resonance imaging after manganese injection distinguishes type 2 diabetic and normoglycemic patients. Islets 4:243–248

    Article  PubMed Central  PubMed  Google Scholar 

  • Bottazzo GF, Dean BM, McNally JM et al (1985) In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med 313:353–360

    Article  PubMed  CAS  Google Scholar 

  • Bremer C, Bredow S, Mahmood U et al (2001) Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model. Radiology 221:523–529

    Article  PubMed  CAS  Google Scholar 

  • Bremer C, Ntziachristos V, Weitkamp B et al (2005) Optical imaging of spontaneous breast tumors using protease sensing ‘smart’ optical probes. Invest Radiol 40:321–327

    Article  PubMed  CAS  Google Scholar 

  • 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 37:1345–1355

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Danaei G, Finucane MM, Lu Y et al (2011) National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378:31–40

    Article  PubMed  CAS  Google Scholar 

  • Danila D, Partha R, Elrod DB et al (2009) Antibody-labeled liposomes for CT imaging of atherosclerotic plaques: in vitro investigation of an anti-ICAM antibody-labeled liposome containing iohexol for molecular imaging of atherosclerotic plaques via computed tomography. Tex Heart Inst J 36:393–403

    PubMed Central  PubMed  Google Scholar 

  • Denis MC, Mahmood U, Benoist C et al (2004) Imaging inflammation of the pancreatic islets in type 1 diabetes. Proc Natl Acad Sci U S A 101:12634–12639

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Eriksson AU, Svensson C, Hornblad A et al (2013) Near infrared optical projection tomography for assessments of beta-cell mass distribution in diabetes research. J Vis Exp 17:e50238

    Google Scholar 

  • Falk GW (2009) Autofluorescence endoscopy. Gastrointest Endosc Clin N Am 19:209–220

    Article  PubMed  Google Scholar 

  • Figueiredo JL, Alencar H, Weissleder R et al (2006) Near infrared thoracoscopy of tumoral protease activity for improved detection of peripheral lung cancer. Int J Cancer 118:2672–2677

    Article  PubMed  CAS  Google Scholar 

  • Fu W, Wojtkiewicz G, Weissleder R et al (2012) Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging. Nat Immunol 13:361–368

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gimi B, Leoni L, Oberholzer J, Braun M, Avila J, Wang Y, Desai T, Philipson LH, Magin RL, Roman BB (2006) Functional MR microimaging of pancreatic beta-cell activation. Cell Transplant 15:195–203

    Article  PubMed  Google Scholar 

  • 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 50:382–389

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Grossman EJ, Lee DD, Tao J et al (2010) Glycemic control promotes pancreatic beta-cell regeneration in streptozotocin-induced diabetic mice. PLoS One 5:e8749

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gupta H, Weissleder R (1996) Targeted contrast agents in MR imaging. Magn Reson Imaging Clin N Am 4:171–184

    PubMed  CAS  Google Scholar 

  • Hangiandreou NJ (2003) AAPM/RSNA physics tutorial for residents. Topics in US: B-mode US: basic concepts and new technology. Radiographics 23:1019–1033

    Article  PubMed  Google Scholar 

  • Hara M, Dizon RF, Glick BS et al (2006) Imaging pancreatic beta-cells in the intact pancreas. Am J Physiol Endocrinol Metab 290:E1041–E1047

    Article  PubMed  CAS  Google Scholar 

  • Harris PE, Farwell MD, Ichise M (2013) PET quantification of pancreatic VMAT 2 binding using (+) and (−) enantiomers of [(1)(8)F]FP-DTBZ in baboons. Nucl Med Biol 40:60–64

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hill ML, Corbin IR, Levitin RB et al (2010) In vitro assessment of poly-iodinated triglyceride reconstituted low-density lipoprotein: initial steps toward CT molecular imaging. Acad Radiol 17:1359–1365

    Article  PubMed  Google Scholar 

  • Imagawa A, Hanafusa T, Tamura S et al (2001) Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes: close correlation between serological markers and histological evidence of cellular autoimmunity. Diabetes 50:1269–1273

    Article  PubMed  CAS  Google Scholar 

  • Jaffer FA, Weissleder R (2004) Seeing within: molecular imaging of the cardiovascular system. Circ Res 94:433–445

    Article  PubMed  CAS  Google Scholar 

  • Judenhofer MS, Wehrl HF, Newport DF, Catana C, Siegel SB, Becker M, Thielscher A, Kneilling M, Lichy MP, Eichner M, Klingel K, Reischl G, Widmaier S, Röcken M, Nutt RE, Machulla HJ, Uludag K, Cherry SR, Claussen CD, Pichler BJ (2008) Simultaneous PET-MRI: a new approach for functional and morphological imaging. Nat Med 4:459–465

    Article  CAS  Google Scholar 

  • Kang NY, Lee SC, Park SJ et al (2013) Visualization and isolation of Langerhans islets by a fluorescent probe PiY. Angew Chem Int Ed Engl 52:8557–8560

    Article  PubMed  CAS  Google Scholar 

  • Katsumata T, Oishi H, Sekiguchi Y et al (2013) Bioluminescence imaging of beta cells and intrahepatic insulin gene activity under normal and pathological conditions. PLoS One 8:e60411

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kircher MF, Willmann JK (2012) Molecular body imaging: MR imaging, CT, and US. Part I. Principles. Radiology 263:633–643

    Article  PubMed Central  PubMed  Google Scholar 

  • Klibanov AL, Rasche PT, Hughes MS et al (2004) Detection of individual microbubbles of ultrasound contrast agents: imaging of free-floating and targeted bubbles. Invest Radiol 39:187–195

    Article  PubMed  Google Scholar 

  • Lamprianou S, Immonen R, Nabuurs C, Gjinovci A, Vinet L, Montet XC, Gruetter R, Meda P (2011) High-resolution magnetic resonance imaging quantitatively detects individual pancreatic islets. Diabetes 60:2853–2860

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lange N, Becker CD, Montet X (2008) Molecular imaging in a (pre-) clinical context. Acta Gastroenterol Belg 71:308–317

    PubMed  Google Scholar 

  • Lebastchi J, Herold KC (2012) Immunologic and metabolic biomarkers of beta-cell destruction in the diagnosis of type 1 diabetes. Cold Spring Harb Perspect Med 2:a007708

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Leoni L, Roman BB (2010) MR imaging of pancreatic islets: tracking isolation, transplantation and function. Curr Pharm Des 16:1582–1594

    Article  PubMed  CAS  Google Scholar 

  • Leoni L, Serai SD, Haque ME et al (2010) Functional MRI characterization of isolated human islet activation. NMR Biomed 23:1158–1165

    Article  PubMed  Google Scholar 

  • Li J, Chaudhary A, Chmura SJ et al (2010) A novel functional CT contrast agent for molecular imaging of cancer. Phys Med Biol 55:4389–4397

    Article  PubMed  Google Scholar 

  • Lin YJ, Koretsky AP (1997) Manganese ion enhances T1-weighted MRI during brain activation: an approach to direct imaging of brain function. Magn Reson Med 38:378–388

    Article  PubMed  CAS  Google Scholar 

  • Lin Y, Sun Z (2010) Current views on type 2 diabetes. J Endocrinol 204:1–11

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Maahs DM, West NA, Lawrence JM et al (2010) Epidemiology of type 1 diabetes. Endocrinol Metab Clin North Am 39:481–497

    Article  PubMed Central  PubMed  Google Scholar 

  • Marchetti P, Bugliani M, Boggi U et al (2012) The pancreatic beta cells in human type 2 diabetes. Adv Exp Med Biol 771:288–309

    PubMed  Google Scholar 

  • Mayo-Smith WW, Schima W, Saini S, Slater GJ, McFarland EG (1998) Pancreatic enhancement and pulse sequence analysis using low-dose mangafodipir trisodium. AJR Am J Roentgenol 170:649–652

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Monici M (2005) Cell and tissue autofluorescence research and diagnostic applications. Biotechnol Annu Rev 11:227–256

    Article  PubMed  CAS  Google Scholar 

  • Montet X, Montet-Abou K, Reynolds F et al (2006a) Nanoparticle imaging of integrins on tumor cells. Neoplasia 8:214–222

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Montet X, Weissleder R, Josephson L (2006b) Imaging pancreatic cancer with a peptide-nanoparticle conjugate targeted to normal pancreas. Bioconjug Chem 17:905–911

    Article  PubMed  CAS  Google Scholar 

  • Montet-Abou K, Viallon M, Hyacinthe JN et al (2010) The role of imaging and molecular imaging in the early detection of metabolic and cardiovascular dysfunctions. Int J Obes (Lond) 34(Suppl 2):S67–S81

    Article  CAS  Google Scholar 

  • Moore A, Sun PZ, Cory D et al (2002) MRI of insulitis in autoimmune diabetes. Magn Reson Med 47:751–758

    Article  PubMed  Google Scholar 

  • Moore A, Grimm J, Han B et al (2004) Tracking the recruitment of diabetogenic CD8+ T-cells to the pancreas in real time. Diabetes 53:1459–1466

    Article  PubMed  CAS  Google Scholar 

  • Normandin MD, Petersen KF, Ding YS et al (2012) In vivo imaging of endogenous pancreatic beta-cell mass in healthy and type 1 diabetic subjects using 18 F-fluoropropyl-dihydrotetrabenazine and PET. J Nucl Med 53:908–916

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ntziachristos V (2010) Going deeper than microscopy: the optical imaging frontier in biology. Nat Methods 7:603–614

    Article  PubMed  CAS  Google Scholar 

  • Orban T, Sosenko JM, Cuthbertson D et al (2009) Pancreatic islet autoantibodies as predictors of type 1 diabetes in the diabetes prevention trial-type 1. Diabetes Care 32:2269–2274

    Article  PubMed Central  PubMed  Google Scholar 

  • Pochon S, Tardy I, Bussat P et al (2010) BR55: a lipopeptide-based VEGFR2-targeted ultrasound contrast agent for molecular imaging of angiogenesis. Invest Radiol 45:89–95

    Article  PubMed  CAS  Google Scholar 

  • Rahier J, Guiot Y, Goebbels RM et al (2008) Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab 10(Suppl 4):32–42

    Article  PubMed  Google Scholar 

  • 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 USA 108:12815–12820

    Article  PubMed Central  PubMed  Google Scholar 

  • Reuveni T, Motiei M, Romman Z et al (2011) Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study. Int J Nanomedicine 6:2859–2864

    PubMed Central  PubMed  CAS  Google Scholar 

  • Rorsman P, Berggren PO, Hellman B (1982) Manganese accumulation in pancreatic beta-cells and its stimulation by glucose. Biochem J 15:435–444

    Google Scholar 

  • Selvaraju RK, Velikyan I, Johansson L, Wu Z, Todorov I, Shively J, Kandeel F, Korsgren O, Eriksson O (2013) In vivo imaging of the glucagonlike peptide 1 receptor in the pancreas with 68Ga-labeled DO3A-Exendin-4. J Nucl Med 8:1458–1463

    Article  CAS  Google Scholar 

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

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Singhal T, Ding YS, Weinzimmer D et al (2011) Pancreatic beta cell mass PET imaging and quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in rodent models of diabetes. Mol Imaging Biol 13:973–984

    Article  PubMed Central  PubMed  Google Scholar 

  • 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 Invest 116:1506–1513

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Vats D, Wang H, Esterhazy D et al (2012) Multimodal imaging of pancreatic beta cells in vivo by targeting transmembrane protein 27 (TMEM27). Diabetologia 55:2407–2416

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Virostko J, Henske J, Vinet L, Lamprianou S, Dai C, Radhika A, Baldwin RM, Ansari MS, Hefti F, Skovronsky D, Kung HF, Herrera PL, Peterson TE, Meda P, Powers AC (2011) Multimodal image coregistration and inducible selective cell ablation to evaluate imaging ligands. Proc Natl Acad Sci U S A 108:20719–20724

    Article  PubMed Central  PubMed  Google Scholar 

  • Virostko J, Radhika A, Poffenberger G et al (2013) Bioluminescence imaging reveals dynamics of beta cell loss in the non-obese diabetic (NOD) mouse model. PLoS One 8:e57784

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wang RK (2002) Signal degradation by multiple scattering in optical coherence tomography of dense tissue: a Monte Carlo study towards optical clearing of biotissues. Phys Med Biol 47:2281–2299

    Article  PubMed  Google Scholar 

  • Wang LV, Hu S (2012) Photoacoustic tomography: in vivo imaging from organelles to organs. Science 335:1458–1462

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Weissleder R (2006) Molecular imaging in cancer. Science 312:1168–1171

    Article  PubMed  CAS  Google Scholar 

  • Wild S, Roglic G, Green A et al (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053

    Article  PubMed  Google Scholar 

  • Willmann JK, Paulmurugan R, Chen K et al (2008) US imaging of tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice. Radiology 246:508–518

    Article  PubMed  Google Scholar 

  • Wu Z, Liu S, Hassink M, Nair I, Park R, Li L, Todorov I, Fox JM, Li Z, Shively JE, Conti PS, Kandeel F (2013) Development and evaluation of 18 F-TTCO-Cys40-Exendin-4: a PET probe for imaging transplanted islets. J Nucl Med 54:244–251

    Article  PubMed  CAS  Google Scholar 

  • Wyss C, Schaefer SC, Juillerat-Jeanneret L et al (2009) Molecular imaging by micro-CT: specific E-selectin imaging. Eur Radiol 19:2487–2494

    Article  PubMed  Google Scholar 

  • Yin H, Park SY, Wang XJ et al (2013) Enhancing pancreatic Beta-cell regeneration in vivo with pioglitazone and alogliptin. PLoS One 8:e65777

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zhang Y, Chen W (2012) Radiolabeled glucagon-like peptide-1 analogues: a new pancreatic beta-cell imaging agent. Nucl Med Commun 33:223–227

    Article  PubMed  CAS  Google Scholar 

  • Zhang B, Yang B, Zhai C et al (2013) The role of exendin-4-conjugated superparamagnetic iron oxide nanoparticles in beta-cell-targeted MRI. Biomaterials 34:5843–5852

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the Swiss National Science Foundation (310000-109402, CR32I3_129987), the Juvenile Diabetes Research Foundation (40-2011-11, 99-2012-775), the European Union (BETAIMAGE 222980, IMIDIA 155055, BETATRAIN 289932), the Fondation Romande pour le Diabète, and the Boninchi Foundation.

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  1. Responsable d’unité, HUG – Hôpitaux Universitaires de Genève, Médecin-Adjoint agrégé, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva 4, Switzerland

    Dr. Xavier Montet

  2. Department of radiology, Geneva University Hospital, Geneva, Switzerland

    Dr. Smaragda Lamprianou, Dr. Laurent Vinet, Dr. Paolo Meda & Dr. Alfredo Fort

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  1. Dr. Xavier Montet
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  2. Dr. Smaragda Lamprianou
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  3. Dr. Laurent Vinet
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  4. Dr. Paolo Meda
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Correspondence to Xavier Montet .

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  1. Södersjukhuset, Karolinska Institutet Dept. Clinical Research & Education, Stockholm, Sweden

    Md. Shahidul Islam

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Montet, X., Lamprianou, S., Vinet, L., Meda, P., Fort, A. (2014). Approaches for Imaging Pancreatic Islets: Recent Advances and Future Prospects. In: Islam, M. (eds) Islets of Langerhans, 2. ed.. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6884-0_39-2

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