Imaging of β-cell mass and insulitis in insulin-dependent (type 1) diabetes mellitus

Endocrine Reviews

Volumn 33, Issue 6, 2012, Pages 892-919

  Di Gialleonardo, Valentina ^a,b   de Vries, Erik F J ^a   Di Girolamo, Marco ^b   Quintero, Ana M ^c   Dierckx, Rudi A J O ^a   Signore, Alberto ^a,b  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c Department of Radiology   (Colombia)

Author keywords

[No Author keywords available]

Indexed keywords

4 FLUOROBENZYLTROZAMICOL; 5 HYDROXYTRYPTOPHAN; ADENOSINE TRIPHOSPHATE; CARBON 11; DIHYDROTETRABENAZINE; DITHIZONE; DOPAMINE; EXENDIN 3; FLUORINE 18; FLUORODEOXYGLUCOSE F 18; GADOBENIC ACID; GADOLINIUM PENTETATE; GLIBENCLAMIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GREEN FLUORESCENT PROTEIN; INTERLEUKIN 2; LEVODOPA; MANGANESE; MONOCRYSTALLINE IRON OXIDE NANOPARTICLE; NAPHTHYLALANINE DERIVATIVE; NEUROTRANSMITTER; NICOTINAMIDE; POTASSIUM CHANNEL; REPAGLINIDE; SEROTONIN; SULFONYLUREA RECEPTOR 1; SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLE; UNCLASSIFIED DRUG; VESICULAR ACETYLCHOLINE TRANSPORTER; VESICULAR MONOAMINE TRANSPORTER 2;

ARTICLE; BIOLUMINESCENCE; COMPUTER ASSISTED TOMOGRAPHY; DIAGNOSTIC IMAGING; DISEASE SEVERITY; DRUG HALF LIFE; FLUORESCENCE; FLUORESCENCE IMAGING; HUMAN; IMMUNOTHERAPY; INSULIN DEPENDENT DIABETES MELLITUS; INSULITIS; KIDNEY PANCREAS TRANSPLANTATION; LYMPHOCYTE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PANCREAS ISLET BETA CELL; PANCREAS ISLET TRANSPLANTATION; PANCREAS TRANSPLANTATION; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; SECRETORY VESICLE; TISSUE HARMONIC IMAGING; ULTRASOUND;

DIABETES MELLITUS, TYPE 1; DIAGNOSTIC IMAGING; HUMANS; INSULIN-SECRETING CELLS;

EID: 84870985165     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.2011-1041     Document Type: Article

References (200)

1. Achenbach P, Bonifacio E, Koczwara K, Ziegler AG. 2005 Natural history of type 1 diabetes. Diabetes 54(Suppl 2): S25-S31
2. Faideau B, Larger E, Lepault F, Carel JC, Boitard C. 2005 Role of β-cells in type 1 diabetes pathogenesis. Diabetes 54(Suppl 2): S87-S96
3. Sosenko JM, Palmer JP, Greenbaum CJ, Mahon J, Cowie C, Krischer JP, Chase HP, White NH, Buckingham B, Herold KC, Cuthbertson D, Skyler JS. 2006 Patterns of metabolic progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1. Diabetes Care 29: 643-649
4. Devendra D, Liu E, Eisenbarth GS. 2004 Type 1 diabetes: recent developments. BMJ 328: 750-754
5. Hanafusa T, Imagawa A. 2008 Insulitis in human type 1 diabetes. Ann NY Acad Sci 1150: 297-299
6. Imagawa A, Hanafusa T. 2010 [Fulminant type 1 diabetes mellitus]. Rinsho Byori 58: 216-224 (Japanese)
7. Like AA, Butler L, Williams RM, Appel MC, Weringer EJ, Rossini AA. 1982 Spontaneous autoimmune diabetes mellitus in the BB rat. Diabetes 31(Suppl 1 Pt 2): 7-13
8. Rossini AA, Mordes JP, Pelletier AM, Like AA. 1983 Transfusions of whole blood prevent spontaneous diabetes mellitus in the BB/W rat. Science 219: 975-977
9. Rossini AA. 1983 Immunotherapy for insulin-dependent diabetics? N Engl J Med 308: 333-335
10. Dyrberg T, Nakhooda AF, Baekkeskov S, Lernmark A, Poussier P, Marliss EB. 1982 Islet cell surface antibodies and lymphocyte antibodies in the spontaneously diabetic BB Wistar rat. Diabetes 31: 278-281
11. Delovitch TL, Singh B. 1997 The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity 7: 727-738
12. Shoda LK, Young DL, Ramanujan S, Whiting CC, Atkinson MA, Bluestone JA, Eisenbarth GS, Mathis D, Rossini AA, Campbell SE, Kahn R, Kreuwel HT. 2005 A comprehensive review of interventions in the NOD mouse and implications for translation. Immunity 23: 115-126
13. Wicker LS, Todd JA, Peterson LB. 1995 Genetic control of autoimmune diabetes in the NOD mouse. Annu Rev Immunol 13: 179-200
14. von Herrath M, Nepom GT. 2009 Animal models of human type 1 diabetes. Nat Immunol 10: 129-132
15. Couri CE, Foss MC, Voltarelli JC. 2006 Secondary prevention of type 1 diabetes mellitus: stopping immune destruction and promoting β-cell regeneration. Braz J Med Biol Res 39: 1271-1280
16. Coppieters K, von Herrath M. 2008 Taking a closer look at the pancreas. Diabetologia 51: 2145-2147
17. Signore A, Chianelli M, Parisella MG, Capriotti G, Giacalone P, Di Leve G, Barone R. 1999 In vivo imaging of insulitis in autoimmune diabetes. J Endocrinol Invest 22: 151-158
18. Souza F, Freeby M, Hultman K, Simpson N, Herron A, Witkowsky P, Liu E, Maffei A, Harris PE. 2006 Current progress in non-invasive imaging of β-cell mass of the endocrine pancreas. Curr Med Chem 13: 2761-2773
19. Wittingen J, Frey CF. 1974 Islet concentration in the head, body, tail and uncinate process of the pancreas. Ann Surg 179: 412-414
20. Saito K, Iwama N, Takahashi T. 1978 Morphometrical analysis on topographical difference in size distribution, number and volume of islets in the human pancreas. Tohoku J Exp Med 124: 177-186
21. Nichols MT, Russ PD, Chen YK. 2006 Pancreatic imaging: current and emerging technologies. Pancreas 33: 211-220
22. Signore A, Mather SJ, Piaggio G, Malviya G, Dierckx RA. 2010 Molecular imaging of inflammation/infection: nuclear medicine and optical imaging agents and methods. Chem Rev 110: 3112-3145
23. Sweet IR, Cook DL, Lernmark A, Greenbaum CJ, Krohn KA. 2004 Non-invasive imaging of β-cell mass: a quantitative analysis. Diabetes Technol Ther 6: 652-659
24. Medarova Z, Moore A. 2009 MRI in diabetes: first results. AJR Am J Roentgenol. 193: 295-303
25. Medarova Z, Castillo G, Dai G, Bolotin E, Bogdanov A, Moore A. 2007 Noninvasive magnetic resonance imaging of microvascular changes in type 1 diabetes. Diabetes 56: 2677-2682
26. Turvey SE, Swart E, Denis MC, Mahmood U, Benoist C, Weissleder R, Mathis D. 2005 Noninvasive imaging of pancreatic inflammation and its reversal in type 1 diabetes. J Clin Invest 115: 2454-2461
27. Granot D, Shapiro EM. 2011 Release activation of iron oxide nanoparticles: (REACTION) A novel environmentally sensitive MRI paradigm. Magn Reson Med 65: 1253-1259
28. Bulte JW, Ma LD, Magin RL, Kamman RL, Hulstaert CE, Go KG, The TH, de Leij L. 1993 Selective MR imaging of labeled human peripheral blood mononuclear cells by liposome mediated incorporation of dextran-magnetite particles. Magn Reson Med 29: 32-37
29. Dodd CH, Hsu HC, Chu WJ, Yang P, Zhang HG, Mountz Jr JD, Zinn K, Forder J, Josephson L, Weissleder R, Mountz JM, Mountz JD. 2001 Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles. J Immunol Methods 256: 89-105
30. Moore A, Sun PZ, Cory D, Högemann D, Weissleder R, Lipes MA. 2002 MRI of insulitis in autoimmune diabetes. Magn Reson Med 47: 751-758
31. Moore A, Grimm J, Han B, Santamaria P. 2004 Tracking the recruitment of diabetogenic CD8β T-cells to the pancreas in real time. Diabetes 53: 1459-1466
32. Gaglia JL, Guimaraes AR, Harisinghani M, Turvey SE, Jackson R, Benoist C, Mathis D, Weissleder R. 2011 Noninvasive imaging of pancreatic islet inflammation in type 1A diabetes patients. J Clin Invest 121: 442-445
33. 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 β-cell activation. Cell Transplant 15: 195-203
34. Jirák D, Kríz J, Herynek V, Andersson B, Girman P, Burian M, Saudek F, Hájek M. 2004 MRI of transplanted pancreatic islets. Magn Reson Med 52: 1228-1233
35. Ris F, Lepetit-Coiffe M, Meda P, Crowe LA, Toso C, Armanet M, Niclauss N, Parnaud G, Giovannoni L, Bosco D, Morel P, Vallee JP, Berney T. 2010 Assessment of human islet labeling with clinical grade iron nanoparticles prior to transplantation for graft monitoring by MRI. Cell Transplant. 19: 1573-1585
36. Toso C, Vallee JP, Morel P, Ris F, Demuylder-Mischler S, Lepetit-Coiffe M, Marangon N, Saudek F, James Shapiro AM, Bosco D, Berney T. 2008 Clinical magnetic resonance imaging of pancreatic islet grafts after iron nanoparticle labeling. Am J Transplant 8: 701-706
37. Kriz J, Jirák D, Girman P, Berková Z, Zacharovova K, Honsova E, Lodererova A, Hajek M, Saudek F. 2005 Magnetic resonance imaging of pancreatic islets in tolerance and rejection. Transplantation 80: 1596-1603
38. Crowe LA, Ris F, Nielles-Vallespin S, Speier P, Masson S, Armanet M, Morel P, Toso C, Bosco D, Berney T, Vallee JP. 2011 A novel method for quantitative monitoring of transplanted islets of langerhans by positive contrast magnetic resonance imaging. Am J Transplant 11: 1158-1168
39. Jung MJ, Lee SS, Hwang YH, Jung HS, Hwang JW, Kim MJ, Yoon S, Lee DY. 2011 MRI of transplanted surfacelabeled pancreatic islets with heparinized superparamagnetic iron oxide nanoparticles. Biomaterials 32: 9391-9400
40. Herynek V, Berková Z, Dovolilová E, Jirák D, Køíž J, Girman P, Saudek F, Hájek M. 2011 Improved detection of pancreatic islets in vivo using double contrast. Contrast Media Mol Imaging 6: 308-313
41. 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
42. Silva ME, Vezozzo DP, Ursich MJ, Rocha DM, Cerri GG, Wajchenberg BL. 1993 Ultrasonographic abnormalities of the pancreas in IDDM and NIDDM patients. Diabetes Care 16: 1296-1297
43. Alzaid A, Aideyan O, Nawaz S. 1993 The size of the pancreas in diabetes mellitus. Diabet Med 10: 759-763
44. Stella SM, Giunta S, Di Cianni G, Benzi L, Galetta F, Cini G, Giusti C. 1993 [The pancreas in diabetes mellitus. The echographic aspects]. Radiol Med 85: 70-74 (Italian)
45. Bhargava R, Senior PA, Ackerman TE, Ryan EA, Paty BW, Lakey JR, ShapiroAM. 2004 Prevalence of hepatic steatosis after islet transplantation and its relation to graft function. Diabetes 53: 1311-1317
46. Harvey CJ, Pilcher JM, Eckersley RJ, Blomley MJ, Cosgrove DO. 2002 Advances in ultrasound. Clin Radiol 57: 157-177
47. Schiemann U, Dieterle C, Götzberger M, Landgraf R, Heldwein W. 2003 Improved ultrasound examination of pancreas grafts in type 1 (insulin-dependent) diabetic patients using tissue harmonic imaging. Transplant Proc 35: 3081-3084
48. Stanley JH, Schabel SI, Seymour EQ, Gobien RP, Vujic I, Ross P. 1983 Pancreatic imaging. South Med J 76: 625-631
49. Goda K, Sasaki E, Nagata K, Fukai M, Ohsawa N, HahafusaT. 2001 Pancreatic volume in type 1 and type 2 diabetes mellitus. Acta Diabetol 38: 145-149
50. Silva AC, Morse BG, Hara AK, Paden RG, Hongo N, Pavlicek W. 2011 Dual-energy (spectral) CT: applications in abdominal imaging. Radiographics 31: 1031-1046; discussion 1047-1050
51. Neri E, Cappelli C, Boggi U, Salvatori L, Vistoli F, Del Chiaro M, Coletti L, Mosca F, Bartolozzi C. 2004 Multirow CT in the follow-up of pancreas transplantation. Transplant Proc 36: 597-600
52. Park SY, Bell GI. 2009 Noninvasive monitoring of changes in pancreatic β-cell mass by bioluminescent imaging in MIP-luc transgenic mice. Horm Metab Res 41: 1-4
53. Park SY, Wang X, Chen Z, Powers AC, Magnuson MA, Head WS, Piston DW, Bell GI. 2005 Optical imaging of pancreatic β-cells in living mice expressing a mouse insulin I promoter-firefly luciferase transgene. Genesis 43: 80-86
54. Chen X, Zhang X, Larson CS, Baker MS, Kaufman DB. 2006 In vivo bioluminescence imaging of transplanted islets and early detection of graft rejection. Transplantation 81: 1421-1427
55. Timpson P, McGhee EJ, Anderson KI. 2011 Imaging molecular dynamics in vivo: from cell biology to animal models. J Cell Sci 124: 2877-2890
56. Kumar AT. 2011 Fluorescence lifetime-based optical molecular imaging. Methods Mol Biol 680: 165-180
57. Yang X, Gong H, Fu J, Quan G, Huang C, Luo Q. 2012 Molecular imaging of small animals with fluorescent proteins: From projection to multimodality. Comput Med Imaging Graph 36: 259-263
58. Crivat G, Taraska JW. 2012 Imaging proteins inside cells with fluorescent tags. Trends Biotechnol 30: 8-16
59. Giepmans BN, Adams SR, Ellisman MH, Tsien RY. 2006 The fluorescent toolbox for assessing protein location and function. Science 312: 217-224
60. Rao J, Dragulescu-Andrasi A, Yao H. 2007 Fluorescence imaging in vivo: recent advances. Curr Opin Biotechnol 18: 17-25
61. Gunawardana SC, Hara M, Bell GI, Head WS, Magnuson MA, Piston DW. 2005 Imaging β-cell development in realtime using pancreatic explants from mice with green fluorescent protein-labeled pancreaticβ-cells. In Vitro Cell Dev Biol Anim 41: 7-11
62. Hara M, Dizon RF, Glick BS, Lee CS, Kaestner KH, Piston DW, Bindokas VP. 2006 Imaging pancreatic β-cells in the intact pancreas. Am J Physiol Endocrinol Metab 290: E1041-E1047
63. Moede T, Leibiger B, Berggren PO, Leibiger IB. 2001 Online monitoring of stimulus-induced gene expression in pancreatic β-cells. Diabetes 50(Suppl 1): S15-S19
64. Hara M, Wang X, Kawamura T, Bindokas VP, Dizon RF, Alcoser SY, Magnuson MA, Bell GI. 2003 Transgenic mice with green fluorescent protein-labeled pancreatic β-cells. Am J Physiol Endocrinol Metab 284: E177-E183
65. Reiner T, Thurber G, Gaglia J, Vinegoni C, Liew CW, Upadhyay R, Kohler RH, Li L, Kulkarni RN, Benoist C, Mathis D, Weissleder R. 2011 Accurate measurement of pancreatic islet β-cell mass using a second-generation fluorescent exendin-4 analog. Proc Natl Acad Sci USA 108: 12815-12820
66. Dodson G, SteinerD. 1998 The role of assembly in insulin's biosynthesis. Curr Opin Struct Biol 8: 189-194
67. Chausmer AB. 1998 Zinc, insulin and diabetes. J Am Coll Nutr 17: 109-115
68. Latif ZA, Noel J, Alejandro R. 1988 A simple method of staining fresh and cultured islets. Transplantation 45: 827-830
69. Fiedor P, Rowin{ogonek} ski W, Licin{ogonek} ska I, Mazurek AP, HardyMA. 1995 The survival identification of pancreatic islets of Langerhans. In vitro and in vivo effects of two dithizone preparations on staining of rat and human islets of Langerhans-preliminary study (part I). Acta Pol Pharm 52: 431-436
70. Epand RM, Stafford AR, Tyers M, Nieboer E. 1985 Mechanism of action of diabetogenic zinc-chelating agents. Model system studies. Mol Pharmacol 27: 366-374
71. Fiedor PS, Oluwole SF, Hardy MA. 1996 Localization of endocrine pancreatic islets. World J Surg. 20: 1016-1022; discussion 1022-1023
72. Garnuszek P, Licin{ogonek} ska I, Fiedor P, Mazurek AP. 1998 The synthesis, radioiodination and preliminary biological study of the new carboxylic derivatives of dithizone. Appl Radiat Isot 49: 1563-1571
73. Sweet IR, Cook DL, Lernmark A, Greenbaum CJ, Wallen AR, Marcum ES, Stekhova SA, KrohnKA. 2004 Systematic screening of potential β-cell imaging agents. Biochem Biophys Res Commun 314: 976-983
74. Toroptsev IV, Eshchenko VA. 1983 [Damaging action of dithizone on insulin-releasing cells]. Biull Eksp Biol Med 96: 23-25 (Russian)
75. Hansen JB. 2006 Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. Curr Med Chem 13: 361-376
76. Kawaki J, Nagashima K, Tanaka J, Miki T, Miyazaki M, Gonoi T, Mitsuhashi N, Nakajima N, Iwanaga T, Yano H, Seino S. 1999 Unresponsiveness to glibenclamide during chronic treatment induced by reduction of ATP-sensitive Kβ channel activity. Diabetes 48: 2001-2006
77. Gribble FM, Reimann F. 2003 Differential selectivity of insulin secretagogues: mechanisms, clinical implications, and drug interactions. J Diabetes Complications 17(2 Suppl): 11-15
78. Murphy R, Ellard S, Hattersley AT. 2008 Clinical implications of a molecular genetic classification of monogenic β-cell diabetes. Nat Clin Pract Endocrinol Metab 4: 200-213
79. Proks P, Reimann F, Green N, Gribble F, Ashcroft F. 2002 Sulfonylurea stimulation of insulin secretion. Diabetes 51(Suppl 3): S368-S376
80. Hansen AM, Christensen IT, Hansen JB, Carr RD, Ashcroft FM, Wahl P. 2002 Differential interactions of nateglinide and repaglinide on the human β-cell sulphonylurea receptor 1. Diabetes 51: 2789-2795
81. Hansen AM, Hansen JB, Carr RD, Ashcroft FM, Wahl P. 2005 Kir6.2-dependent high-affinity repaglinide binding to β-cell K(ATP) channels. Br J Pharmacol 144: 551-557
82. Wängler B, Beck C, Shiue CY, Schneider S, Schwanstecher C, Schwanstecher M, Feilen PJ, Alavi A, Rösch F, Schirrmacher R. 2004 Synthesis and in vitro evaluation of (S)-2-([11C] methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butylcarbam oyl]-benzoic acid ([11C]methoxy-repaglinide): a potential β-cell imaging agent. Bioorg Med Chem Lett 14: 5205-5209
83. 18F]repaglinide): a promising radioligand for quantification of pancreatic β-cell mass with positron emission tomography (PET). Nucl Med Biol 31: 639-647
84. Mikhailov MV, Mikhailova EA, Ashcroft SJ. 2001 Molecular structure of the glibenclamide binding site of theβ-cell K(ATP) channel. FEBS Lett 499: 154-160
85. Wolffenbuttel BH, Graal MB. 1996 New treatments for patients with type 2 diabetes mellitus. Postgrad Med J 72: 657-662
86. Hambrock A, Löffler-Walz C, Quast U. 2002 Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides. Br J Pharmacol 136: 995-1004
87. 18 labeled glyburide analogs as β-cell imaging agents. Nucl Med Biol 31: 483-491
88. Schneider S, Ueberberg S, Korobeynikov A, Schechinger W, Schwanstecher C, Schwanstecher M, Klein HH, Schirrmacher E. 2007 Synthesis and evaluation of a glibenclamide glucose-conjugate: a potential new lead compound for substituted glibenclamide derivatives as islet imaging agents. Regul Pept 139: 122-127
89. Papotti M, Bongiovanni M, Volante M, Allìa E, Landolfi S, Helboe L, Schindler M, Cole SL, Bussolati G. 2002 Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. Virchows Arch 440: 461-475
90. Sundin A, Garske U, Orlefors H. 2007 Nuclear imaging of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 21: 69-85
91. 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 39: 72-82
92. 68Ga-DOTAlanreotide positron emission tomography. Q J Nucl Med Mol Imaging 54: 52-60
93. Thakur M, Kolan H, Rifat S, Li J, Rux A, John E, Halmos G, Schally A. 1996 Vapreotide labeled with Tc-99m for imaging tumors. Int J Oncol 9: 445-451
94. Amartey JK, Esguerra C, Al-Jammaz I, Parhar RS, Al-Otaibi B. 2006 Synthesis and evaluation of radioiodinated substitutedβ-naphthylalanine as a potential probe for pancreatic β-cells imaging. Appl Radiat Isot 64: 769-777
95. Amartey JK, Shi Y, Al-Jammaz I, Esguerra C, Al-Otaibi B, Al-Mohanna F. 2008 Radioiodinated naphthylalanine derivatives targeting pancreatic β-cells in normal and nonobese diabetic mice. Exp Diabetes Res. 2008: 371716
96. Kalinderi K, Fidani L, Katsarou Z, Bostantjopoulou S. 2011 Pharmacological treatment and the prospect of pharmacogenetics in Parkinson's disease. Int J Clin Pract 65: 1289-1294
97. Lewitt PA. 2008 Levodopa for the treatment of Parkinson's disease. N Engl J Med 359: 2468-2476
98. Rascol O, Lozano A, Stern M, PoeweW. 2011 Milestones in Parkinson's disease therapeutics. Mov Disord 26: 1072-1082
99. Hornykiewicz O. 2002 L-DOPA: from a biologically inactive amino acid to a successful therapeutic agent. Amino Acids 23: 65-70
100. Barrio JR, Huang SC, PhelpsME. 1997 Biological imaging and the molecular basis of dopaminergic diseases. Biochem Pharmacol 54: 341-348
101. Shinotoh H, CalneDB. 1995 The use of PET in Parkinson's disease. Brain Cogn 28: 297-310
102. 18F-DOPA PET: a prospective, diagnostic accuracy study. Lancet Oncol 7: 728-734
103. Ekholm R, Ericson LE, Lundquist I. 1971 Monoamines in the pancreatic islets of the mouse. Subcellular localization of 5-hydroxytryptamine by electron microscopic autoradiography. Diabetologia 7: 339-348
104. Ericson LE, Håkanson R, Lundquist I. 1977 Accumulation of dopamine in mouse pancreatic B-cells following injection of L-DOPA. Localization to secretory granules and inhibition of insulin secretion. Diabetologia 13: 117-124
105. Lundquist I, Panagiotidis G, Stenström A. 1991 Effect of L-dopa administration on islet monoamine oxidase activity and glucose-induced insulin release in the mouse. Pancreas 6: 522-527
106. Kirchgessner AL, Gershon MD. 1990 Innervation of the pancreas by neurons in the gut. J Neurosci 10: 1626-1642
107. Portela-Gomes GM, Stridsberg M, Grimelius L, Oberg K, Janson ET. 2000 Expression of the five different somatostatin receptor subtypes in endocrine cells of the pancreas. Appl Immunohistochem Mol Morphol 8: 126-132
108. Saravia F, Homo-Delarche F. 2003 Is innervation an early target in autoimmune diabetes? Trends Immunol 24: 574-579
109. Deeney JT, Bränström R, Corkey BE, Larsson O, Berggren PO. 2007 3H-serotonin as a marker of oscillatory insulin secretion in clonal β-cells (INS-1). FEBS Lett 581: 4080-4084
110. 18F-dihydroxy-phenyl-alanine and 11C-5-hydroxy-tryptophan positron emission tomography. J Clin Oncol 26: 1489-1495
111. 18F]fluoro-3,4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells. Cancer Res 68: 7183-7190
112. Henry JP, Sagné C, Bedet C, Gasnier B. 1998 The vesicular monoamine transporter: from chromaffin granule to brain. Neurochem Int 32: 227-246
113. Anlauf M, Eissele R, Schäfer MK, Eiden LE, Arnold R, Pauser U, Klöppel G, Weihe E. 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: 1027-1040
114. Saisho Y, Harris PE, Butler AE, Galasso R, Gurlo T, Rizza RA, Butler PC. 2008 Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas. J Mol Histol 39: 543-551
115. 18F-FP-(β)-DTBZ: a potential PET ligand for studying diabetes mellitus. J Nucl Med 49: 1171-1176
116. Simpson NR, Souza F, Witkowski P, Maffei A, Raffo A, Herron A, Kilbourn M, Jurewicz A, Herold K, Liu E, Hardy MA, Van Heertum R, Harris PE. 2006 Visualizing pancreatic β-cell mass with [11C]DTBZ. Nucl Med Biol 33: 855-864
117. Souza F, Simpson N, Raffo A, Saxena C, Maffei A, Hardy M, Kilbourn M, Goland R, Leibel R, Mann JJ, Van Heertum R, Harris PE. 2006 Longitudinal noninvasive PETbased β-cell mass estimates in a spontaneous diabetes rat model. J Clin Invest 116: 1506-1513
118. Goland R, Freeby M, Parsey R, Saisho Y, Kumar D, Simpson N, Hirsch J, Prince M, Maffei A, Mann JJ, Butler PC, Van Heertum R, Leibel RL, Ichise M, Harris PE. 2009 11Cdihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med 50: 382-389
119. Harris PE, Ferrara C, Barba P, Polito T, Freeby M, Maffei A. 2008 VMAT2 gene expression and function as it applies to imaging β-cell mass. J Mol Med 86: 5-16
120. +)-DTBZ as a tracer for β-cell mass. Nucl Med Biol 37: 357-363
121. Ahrén B. 2000 Autonomic regulation of islet hormone secretion-implications for health and disease. Diabetologia 43: 393-410
122. Gilon P, Henquin JC. 2001 Mechanisms and physiological significance of the cholinergic control of pancreatic β-cell function. Endocr Rev 22: 565-604
123. 18F]4-fluorobenzyltrozamicol. Eur J Nucl Med Mol Imaging 31: 258-260
124. Bading JR, Shields AF. 2008 Imaging of cell proliferation: status and prospects. J Nucl Med 49(Suppl 2): 64S-80S
125. 18FFDG PET in oncology. J Nucl Med 49: 480-508
126. Toso C, Zaidi H, Morel P, Armanet M, Andres A, Pernin N, Baertschiger R, Slosman D, Bühler LH, Bosco D, Berney T. 2005 Positron-emission tomography imaging of early events after transplantation of islets of Langerhans. Transplantation 79: 353-355
127. Eich T, Eriksson O, Sundin A, Estrada S, Brandhorst D, Brandhorst H, Langstrom B, Nilsson B, Korsgren O, Lundgren T. 2007 Positron emission tomography: a real-time tool to quantify early islet engraftment in a preclinical large animal model. Transplantation 84: 893-898
128. Eriksson O, Eich T, Sundin A, Tibell A, Tufveson G, Andersson H, Felldin M, Foss A, Kyllönen L, Langstrom B, Nilsson B, Korsgren O, Lundgren T. 2009 Positron emission tomography in clinical islet transplantation. Am J Transplant 9: 2816-2824
129. Tjalve H, Wilander E. 1976 The uptake in the pancreatic islets of nicotinamide, nicotinic acid and tryptophan and their ability to prevent streptozotocin diabetes in mice. Acta Endocrinol (Copenh) 83: 357-364
130. Sofue M, Yoshimura Y, Nishida M, Kawada J. 1991 Uptake of nicotinamide by rat pancreatic β-cells with regard to streptozotocin action. J Endocrinol 131: 135-138
131. Ahrén B. 2009 Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes. Nat Rev Drug Discov 8: 369-385
132. Drucker DJ. 2003 Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol 17: 161-171
133. Kieffer TJ, Habener JF. 1999 The glucagon-like peptides. Endocr Rev. 20: 876-913
134. Tornehave D, Kristensen P, Rømer J, Knudsen LB, Heller RS. 2008 Expression of the GLP-1 receptor in mouse, rat, and human pancreas. J Histochem Cytochem 56: 841-851
135. Gotthardt M, Fischer M, Naeher I, Holz JB, Jungclas H, Fritsch HW, Béhé M, Göke B, Joseph K, Behr TM. 2002 Use of the incretin hormone glucagon-like peptide-1 (GLP-1) for the detection of insulinomas: initial experimental results. Eur J Nucl Med Mol Imaging 29: 597-606
136. Brom M, Oyen WJ, Joosten L, Gotthardt M, BoermanOC. 2010 68Ga-labelled exendin-3, a new agent for the detection of insulinomas with PET. Eur J Nucl Med Mol Imaging 37: 1345-1355
137. 111In)NH2]exendin-4, a very promising ligand for glucagon-like peptide-1 (GLP-1) receptor targeting. J Nucl Med 47:. 2025-2033
138. Pattou F, Kerr-Conte J, Wild D. 2010 GLP-1-receptor scanning for imaging of human β-cells transplanted in muscle. N Engl J Med 363: 1289-1290
139. 18F-FBEM-EM3106B, a new GLP-1 analogue. Mol Pharm 8: 1775-1782
140. Blomqvist M, Osterbye T, Månsson JE, Horn T, Buschard K, Fredman P. 2002 Sulfatide is associated with insulin granules and located to microdomains of a cultured β-cell line. Glycoconj J. 19: 403-413
141. Moore A, Bonner-Weir S, Weissleder R. 2001 Noninvasive in vivo measurement of β-cell mass in mouse model of diabetes. Diabetes 50: 2231-2236
142. Saudek F, BrogrenCH, ManoharS. 2008 Imaging theβ-cell mass: why and how. Rev Diabet Stud 5: 6-12
143. 111In improves MORF/cMORF pretargeting by reducing intestinal accumulation. Mol Imaging Biol 11: 303-307
144. 111In-DTPA morpholino oligomer for low abdominal accumulation. Appl Radiat Isot 68: 1709-1714
145. In't Veld P. 2011 Insulitis in human type 1 diabetes: the quest for an elusive lesion. Islets 3: 131-138
146. Bottazzo GF. 1984 β-Cell damage in diabetic insulitis: are we approaching a solution? Diabetologia 26: 241-249
147. Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PG, Gamble DR. 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
148. Foulis AK, Liddle CN, Farquharson MA, Richmond JA, Weir RS. 1986 The histopathology of the pancreas in type 1 (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under. 20 years of age in the United Kingdom. Diabetologia 29: 267-274
149. Gepts W. 1965 Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14: 619-633
150. Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. 2009 Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol 155: 173-181
151. van Belle TL, Coppieters KT, von Herrath MG. 2011 Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev 91: 79-118
152. 111 oxine. Am J Hosp Pharm 37: 847-850
153. 111 oxinelabeled leukocytes for early diagnosis of ischemic enterocolitis. J Pediatr Surg 26: 1039-1042
154. 111In-oxine. Inflammation/Infection Taskgroup of the European Association of Nuclear Medicine. Eur J Nucl Med Mol Imaging 37: 835-841
155. 111 tropolonate leucocyte scanning in the detection of intra-abdominal abscesses. Clin Radiol 34: 593-596
156. 111 tropolonate labeled leukocytes. J Nucl Med 24: 39-44
157. 99mTc-HMPAO for labelling leucocytes in infection. Lancet 1: 44
158. 99mTc-HMPAO. Inflammation/Infection Taskgroup of the European Association of Nuclear Medicine. Eur J Nucl Med Mol Imaging 37: 842-848
159. 99mTc-HMPAO for scintigraphy of inflammatory lesions and abscesses. Int J Rad Appl Instrum B. 19: 251-256
160. Boerman OC, Rennen H, Oyen WJ, Corstens FH. 2001 Radiopharmaceuticals to image infection and inflammation. Semin Nucl Med 31: 286-295
161. Kaldany A, Hill T, Wentworth S, Brink SJ, D'Elia JA, Clouse M, Soeldner JS. 1982 Trapping of peripheral blood lymphocytes in the pancreas of patients with acute-onset insulin-dependent diabetes mellitus. Diabetes 31: 463-466
162. 111Indiumlabelled lymphocytes do not image or label the pancreas of the BB/W rat. Diabetologia 28: 143-147
163. Kono T, Minami Y, Taniguchi T. 1993 The interleukin-2 receptor complex and signal transduction: role of the β-chain. Semin Immunol 5: 299-307
164. Minami Y, Kono T, Miyazaki T, Taniguchi T. 1993 The IL-2 receptor complex: its structure, function, and target genes. Annu Rev Immunol 11: 245-268
165. Feghali CA, Wright TM. 1997 Cytokines in acute and chronic inflammation. Front Biosci 2: d12-d26
166. Signore A, Picarelli A, Chianelli M., Biancone L, Annovazzi A, Tiberti C, Anastasi E, Multari G, Negri M, Pallone F, Pozzilli P. 1996 I-interleukin-2 scintigraphy: a new approach to assess disease activity in autoimmunity. J Pediatr Endocrinol Metab 9(Suppl 1): 139-144
167. Signore A, Beverley PC, Parman A, Negri M, Pozzilli P. 1987 Labelling of interleukin-2 (IL-2) with 123-iodine with retention of its capacity to bind to activated lymphocytes. Exp Clin Endocrinol 89: 301-306
168. Signore A, Parman A, Pozzilli P, Andreani D, Beverley PC. 1987 Detection of activated lymphocytes in endocrine pancreas of BB/W rats by injection of 123I-interleukin-2: an early sign of type 1 diabetes. Lancet 2: 537-540
169. Signore A, Chianelli M, Toscano A, Monetini L, Ronga G, Nimmon CC, Britton KE, Pozzilli P, Negri M. 1992 A radiopharmaceutical for imaging areas of lymphocytic infiltration: 123I-interleukin-2. Labelling procedure and animal studies. Nucl Med Commun 13: 713-722
170. Signore A, Chianelli M, Ferretti E, Toscano A, Britton KE, Andreani D, Gale EA, Pozzilli P. 1994 New approach for in vivo detection of insulitis in type I diabetes: activated lymphocyte targeting with 123I-labelled interleukin 2. Eur J Endocrinol 131: 431-437
171. 99m-labelled interleukin-2: a new radiopharmaceutical for the in vivo detection of mononuclear cell infiltrates in immune-mediated diseases. Nucl Med Biol 24: 579-586
172. 99mTc-interleukin-2 at diagnosis of type 1 diabetes and after 1 year of nicotinamide therapy. Diabetes Metab Res Rev 24: 115-122
173. 99mTc-interleukin-2 scintigraphy in normal subjects and in patients with autoimmune thyroid diseases: a feasibility study. Eur J Nucl Med Mol Imaging 35: 2286-2293
174. 99mTc-HYNIC-interleukin-2 for in vivo imaging of activated T lymphocytes. Mol Imaging Biol 12: 539-546
175. 18F-Fluorobenzoyl)interleukin-2 for PET of human-activated T lymphocytes. J Nucl Med 53: 679-686
176. Signore A, Barone R, Procaccini E, Annovazzi A, Chianelli M, Scopinaro F, Ronga G, Multari G, Looman WJ, Pozzilli P. 1996 In vivo measurement of immunoglobulin accumulation in the pancreas of recent onset type 1 diabetic patients. Clin Exp Rheumatol 14(Suppl 15): S41-S45
177. 99m labelled human polyclonal immunoglobulins in patients with type 1 diabetes. Eur J Nucl Med 25: 503-508
178. Malviya G, D'Alessandria C, Bonanno E, Vexler V, Massari R, Trotta C, Scopinaro F, Dierckx R, Signore A. 2009 Radiolabeled humanized anti-CD3 monoclonal antibody visilizumab for imaging human T-lymphocytes. J Nucl Med 50: 1683-1691
179. 99m labelled specific anti-CD4- and non-specific monoclonal antibodies. Eur J Nucl Med 21: 176-180
180. Marcus C, Thakur ML, Huynh TV, Louie JS, Leibling M, Minami C, Diggles L. 1994 Imaging rheumatic joint diseases with anti-T lymphocyte antibody OKT-3. Nucl Med Commun 15: 824-830
181. Kominsky DJ, Campbell EL, Colgan SP. 2010 Metabolic shifts in immunity and inflammation. J Immunol 184: 4062-4068
182. 18F]FDG uptake to islets of Langerhans in NOD mouse. Diabetes Res Clin Pract 70: 217-224
183. 18F]fluoro-D-glucose in control and diabetic rats. Int J Mol Med 5: 525-532
184. Kalliokoski T, Nuutila P, Virtanen KA, Iozzo P, Bucci M, Svedström E, Roivainen A, Någren K, Viljanen T, Minn H, Knuuti J, Rönnemaa T, Simell O. 2008 Pancreatic glucose uptake in vivo in men with newly diagnosed type 1 diabetes. J Clin Endocrinol Metab 93: 1909-1914
185. 18F-FDG-leukocyte imaging to monitor rejection after pancreatic islet transplantation. Transplant Proc 38: 3033-3034
186. LeCompte PM. 1958 Insulitis in early juvenile diabetes. AMA Arch Pathol 66: 450-457
187. Junker K, Egeberg J, Kromann H, Nerup J. 1977 An autopsy study of the islets of Langerhans in acute-onset ju-venile diabetes mellitus. Acta Pathol Microbiol Scand A 85: 699-706
188. Foulis AK, Stewart JA. 1984 The pancreas in recent-onset type 1 (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue. Diabetologia 26: 456-461
189. Foulis AK, Farquharson MA, Hardman R. 1987 Aberrant expression of class II major histocompatibility complex molecules by B cells and hyperexpression of class I major histocompatibility complex molecules by insulin containing islets in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 333-343
190. Foulis AK, Francis ND, Farquharson MA, Boylston A. 1988 Massive synchronous B-cell necrosis causing type 1 (insulin-dependent) diabetes: a unique histopathological case report. Diabetologia 31: 46-50
191. Hanafusa T, Miyazaki A, Miyagawa J, Tamura S, Inada M, Yamada K, Shinji Y, Katsura H, Yamagata K, Itoh N. 1990 Examination of islets in the pancreas biopsy specimens from newly diagnosed type 1 (insulin-dependent) diabetic patients. Diabetologia 33: 105-111
192. Foulis AK, Farquharson MA, Cameron SO, McGill M, Schönke H, Kandolf R. 1990 A search for the presence of the enteroviral capsid proteinVP1in pancreases of patients with type 1 (insulin-dependent) diabetes and pancreases and hearts of infants who died of coxsackieviral myocarditis. Diabetologia 33: 290-298
193. Itoh N, Hanafusa T, Miyazaki A, Miyagawa J, Yamagata K, Yamamoto K, Waguri M, Imagawa A, Tamura S, Inada M. 1993 Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients. J Clin Invest 92: 2313-2322
194. Somoza N, Vargas F, Roura-Mir C, Vives-Pi M, Fernández-Figueras MT, Ariza A, Gomis R, Bragado R, Martí M, Jaraquemada D. 1994 Pancreas in recent onset insulin-dependent diabetes mellitus. Changes in HLA, adhesion molecules and autoantigens, restricted T cell receptor Vβ usage, and cytokine profile. J Immunol 153: 1360-1377
195. Lernmark A, Klöppel G, Stenger D, Vathanaprida C, Fält K, Landin-Olsson M, Baskin DG, Palmer JP, Gown AM, Petersen JS. 1995 Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus. Virchows Arch 425: 631-640
196. Imagawa A, Hanafusa T, Itoh N, Waguri M, Yamamoto K, Miyagawa J, Moriwaki M, Yamagata K, Iwahashi H, Sada M, Tsuji T, Tamura S, Kawata S, Kuwajima M, Nakajima H, Namba M, Matsuzawa Y. 1999 Immunological abnormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recentonset Type I (insulin-dependent) diabetes mellitus. Diabetologia 42: 574-578
197. Shimada A, Imazu Y, Morinaga S, Funae O, Kasuga A, Atsumi Y, Matsuoka K. 1999 T-cell insulitis found in anti-GAD65β diabetes with residual β-cell function. A case report. Diabetes Care 22: 615-617
198. Imagawa A, Hanafusa T, Tamura S, Moriwaki M, Itoh N, Yamamoto K, Iwahashi H, Yamagata K, Waguri M, Nanmo T, Uno S, Nakajima H, Namba M, Kawata S, Miyagawa JI, Matsuzawa Y. 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
199. Cheung SS, Metzger DL, Wang X, Huang J, Tai J, Tingle AJ, Ou D. 2005 Tumor necrosis factor-related apoptosisinducing ligand and CD56 expression in patients with type 1 diabetes mellitus. Pancreas 30: 105-114
200. 18F-FB-IL2 PET. Eur J Nucl Med Mol Imaging 37(Suppl 2): S198-S311