Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Imaging in pancreatic disease

Key Points

  • Pancreatic cancer is frequently diagnosed after the appearance of symptoms, which is too late for curable treatment

  • No blood test currently exists for chronic pancreatitis and the diagnosis can be difficult to make, even with current imaging technologies

  • Treating pancreatic disease at an early stage of the pathogenesis could lead to better prognosis

  • Currently used imaging techniques have various limitations, including difficulty in discriminating between benign and malignant conditions

  • Molecular imaging can augment conventional imaging modalities for the diagnosis of incipient pancreatic diseases


Pancreatic diseases, chronic pancreatitis, pancreatic cancer and diabetes mellitus, taken together, occur in >10% of the world population. Pancreatic diseases, as with other diseases, benefit from early intervention and appropriate diagnosis. Although imaging technologies have given clinicians an unprecedented toolbox to aid in clinical decision-making, advances in these technologies and development of molecular-based diagnostic tools could enable physicians to identify diseases at an even earlier stage and, thereby, improve patient outcomes. In this Review, we discuss and identify gaps in the use of imaging techniques for the early detection and appropriate treatment stratification of various pancreatic diseases, including diabetes mellitus, acute and chronic pancreatitis and pancreatic cancer. Imaging techniques discussed are MRI, CT, PET and ultrasonography. Additionally, the identification of new molecular targets for imaging and the development of contrast agents that are able to give molecular information in noninvasive radionuclear imaging and ultrasonography are emerging areas of innovation that could lead to increased diagnostic accuracy and improved patient outcomes.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Use of endoscopic ultrasonography in pancreatic lesions.
Figure 2: Use of molecular imaging in experimental pancreatic disease.
Figure 3: Molecular imaging in a mouse model of pancreatic cancer.
Figure 4: PET imaging in experimental pancreatic cancer.
Figure 5: Molecular imaging of experimental diabetes mellitus.
Figure 6: Conceptual view of pancreatic disease imaging.


  1. 1

    Berger, H. G. et al. (eds) The Pancreas (Blackwell Publishing Ltd., 2008)

    Book  Google Scholar 

  2. 2

    Coté, G. A., Smith, J., Sherman, S. & Kelly, K. Technologies for imaging the normal and diseased pancreas. Gastroenterology 144, 1262–1271.e1 (2013).

    Article  PubMed  Google Scholar 

  3. 3

    Li, H., Hu, Z., Chen, J. & Guo, X. Comparison of ERCP, EUS, and ERCP combined with EUS in diagnosing pancreatic neoplasms: a systematic review and meta-analysis. Tumour Biol. 35, 8867–8874 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. 4

    Bushberg, J. T. The Essential Physics of Medical Imaging. (Lippincott Williams & Wilkins, 2002).

    Google Scholar 

  5. 5

    Lindner, J. R. Microbubbles in medical imaging: current applications and future directions. Nat. Rev. Drug Discov. 3, 527–532 (2004).

    Article  CAS  PubMed  Google Scholar 

  6. 6

    Rickes, S. et al. Contrast-enhanced sonography in pancreatic diseases. Eur. J. Radiol. 64, 183–188 (2007).

    Article  PubMed  Google Scholar 

  7. 7

    Barr, R. G. Off-label use of ultrasound contrast agents for abdominal imaging in the United States. J. Ultrasound Med. 32, 7–12 (2013).

    Article  PubMed  Google Scholar 

  8. 8

    Worhunsky, D. J. et al. Pancreatic neuroendocrine tumours: hypoenhancement on arterial phase computed tomography predicts biological aggressiveness. HPB (Oxford) 16, 304–311 (2014).

    Article  Google Scholar 

  9. 9

    D'Onofrio, M., Zamboni, G., Faccioli, N., Capelli, P. & Pozzi Mucelli, R. Ultrasonography of the pancreas. 4. Contrast-enhanced imaging. Abdom. Imaging 32, 171–181 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. 10

    Robles-Medranda, C. Confocal endomicroscopy: is it time to move on? World J. Gastrointest. Endosc. 8, 1–3 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11

    Yachida, S. et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467, 1114–1117 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Diagnosis of Diabetes and Prediabetes | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Available at: (Accessed: 7 December 2015).

  13. 13

    Chen, R., Pan, S., Brentnall, T. A. & Aebersold, R. Proteomic profiling of pancreatic cancer for biomarker discovery. Mol. Cell. Proteom. 4, 523–533 (2005).

    Article  CAS  Google Scholar 

  14. 14

    Farr, R. J., Joglekar, M. V., Taylor, C. J. & Hardikar, A. A. Circulating non-coding RNAs as biomarkers of β cell death in diabetes. Pediatr. Endocrinol. Rev. 11, 14–20 (2013).

    PubMed  Google Scholar 

  15. 15

    Melo, S. A. et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 523, 177–182 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Rhim, A. D. et al. Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions. Gastroenterology 146, 647–651 (2014).

    Article  PubMed  Google Scholar 

  17. 17

    Chari, S. T. et al. Early detection of sporadic pancreatic cancer: summative review. Pancreas 44, 693–712 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18

    Klibanov, A. L. et al. Targeting of ultrasound contrast material. An in vitro feasibility study. Acta Radiol. Suppl. 412, 113–120 (1997).

    CAS  PubMed  Google Scholar 

  19. 19

    Klibanov, A. Targeted delivery of gas-filled microspheres, contrast agents for ultrasound imaging. Adv. Drug Deliv. Rev. 37, 139–157 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. 20

    Foygel, K. et al. Detection of pancreatic ductal adenocarcinoma in mice by ultrasound imaging of thymocyte differentiation antigen 1. Gastroenterology 145, 885–894.e3 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Pogue, B. W., Leblond, F., Krishnaswamy, V. & Paulsen, K. D. Radiologic and near-infrared/optical spectroscopic imaging: where is the synergy? AJR Am. J. Roentgenol. 195, 321–332 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22

    Rudin, M. & Weissleder, R. Molecular imaging in drug discovery and development. Nat. Rev. Drug Discov. 2, 123–131 (2003).

    Article  CAS  PubMed  Google Scholar 

  23. 23

    Whitcomb, D. C. Clinical practice. Acute pancreatitis. N. Engl. J. Med. 354, 2142–2150 (2006).

    Article  PubMed  Google Scholar 

  24. 24

    Lankisch, P. G., Apte, M. & Banks, P. A. Acute pancreatitis. Lancet 386, 85–96 (2015).

    Article  PubMed  Google Scholar 

  25. 25

    Lévy, P., Domínguez-Muñoz, E., Imrie, C., Löhr, M. & Maisonneuve, P. Epidemiology of chronic pancreatitis: burden of the disease and consequences. United European Gastroenterol. J. 2, 345–354 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26

    Olsen, T. S. The incidence and clinical relevance of chronic inflammation in the pancreas in autopsy material. Acta Pathol. Microbiol. Scand. A 86A, 361–365 (1978).

    Article  Google Scholar 

  27. 27

    Shimizu, M., Hayashi, T., Saitoh, Y. & Itoh, H. Interstitial fibrosis in the pancreas. Am. J. Clin. Pathol. 91, 531–534 (1989).

    Article  CAS  PubMed  Google Scholar 

  28. 28

    Stamm, B. H. Incidence and diagnostic significance of minor pathologic changes in the adult pancreas at autopsy: a systematic study of 112 autopsies in patients without known pancreatic disease. Hum. Pathol. 15, 677–683 (1984).

    Article  CAS  PubMed  Google Scholar 

  29. 29

    Whitcomb, D. C. & Pogue-Geile, K. Pancreatitis as a risk for pancreatic cancer. Gastroenterol. Clin. North Am. 31, 663–678 (2002).

    Article  PubMed  Google Scholar 

  30. 30

    Raimondi, S., Lowenfels, A. B., Morselli-Labate, A. M., Maisonneuve, P. & Pezzilli, R. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract. Res. Clin. Gastroenterol. 24, 349–358 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31

    Neff, C. C., Simeone, J. F., Wittenberg, J., Mueller, P. R. & Ferrucci, J. T. Inflammatory pancreatic masses. Problems in differentiating focal pancreatitis from carcinoma. Radiology 150, 35–38 (1984).

    Article  CAS  PubMed  Google Scholar 

  32. 32

    Thoeni, R. F. Imaging of acute pancreatitis. Radiol. Clin. North Am. 53, 1189–1208 (2015).

    Article  PubMed  Google Scholar 

  33. 33

    Bollen, T. L. Acute pancreatitis: international classification and nomenclature. Clin. Radiol 71, 121–133 (2016).

    Article  CAS  PubMed  Google Scholar 

  34. 34

    Singh, V. K. et al. An assessment of the severity of interstitial pancreatitis. Clin. Gastroenterol. Hepatol. 9, 1098–1103 (2011).

    Article  PubMed  Google Scholar 

  35. 35

    van Santvoort, H. C. et al. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome. Gastroenterology 141, 1254–1263 (2011).

    Article  PubMed  Google Scholar 

  36. 36

    Ljutic, D., Piplovic-Vukovic, T., Raos, V. & Andrews, P. Acute renal failure as a complication of acute pancreatitis. Ren. Fail. 18, 629–633 (1996).

    Article  CAS  PubMed  Google Scholar 

  37. 37

    Tenner, S., Baillie, J., DeWitt, J., Vege, S. S. & American College of Gastroenterology American College of Gastroenterology guideline: management of acute pancreatitis. Am. J. Gastroenterol. 108, 1400–1415, 1416 (2013).

    Article  CAS  PubMed  Google Scholar 

  38. 38

    Golea, A., Badea, R., Socaciu, M., Diaconu, B. & Iacob, D. Quantitative analysis of tissue perfusion using contrast-enhanced transabdominal ultrasound (CEUS) in the evaluation of the severity of acute pancreatitis. Med. Ultrason. 12, 198–204 (2010).

    PubMed  Google Scholar 

  39. 39

    Siracusano, S. et al. The current role of contrast-enhanced ultrasound (CEUS) imaging in the evaluation of renal pathology. World J. Urol. 29, 633–638 (2011).

    Article  PubMed  Google Scholar 

  40. 40

    Hasebroock, K. M. & Serkova, N. J. Toxicity of MRI and CT contrast agents. Expert Opin. Drug Metab. Toxicol. 5, 403–416 (2009).

    Article  CAS  PubMed  Google Scholar 

  41. 41

    Ripollés, T., Martínez, M. J., López, E., Castelló, I. & Delgado, F. Contrast-enhanced ultrasound in the staging of acute pancreatitis. Eur. Radiol. 20, 2518–2523 (2010).

    Article  PubMed  Google Scholar 

  42. 42

    Steer, M. L., Waxman, I. & Freedman, S. Chronic pancreatitis. N. Engl. J. Med. 332, 1482–1490 (1995).

    Article  CAS  PubMed  Google Scholar 

  43. 43

    Gumaste, V. V., Roditis, N., Mehta, D. & Dave, P. B. Serum lipase levels in nonpancreatic abdominal pain versus acute pancreatitis. Am. J. Gastroenterol. 88, 2051–2055 (1993).

    CAS  PubMed  Google Scholar 

  44. 44

    Choueiri, N. E., Balci, N. C., Alkaade, S. & Burton, F. R. Advanced Imaging of chronic pancreatitis. Curr. Gastroenterol. Rep. 12, 114–120 (2010).

    Article  PubMed  Google Scholar 

  45. 45

    Siddiqi, A. J. & Miller, F. Chronic pancreatitis: ultrasound, computed tomography, and magnetic resonance imaging features. Semin. Ultrasound CT MRI 28, 384–394 (2007).

    Article  Google Scholar 

  46. 46

    Bali, M. A. et al. Quantification of pancreatic exocrine function with secretin-enhanced magnetic resonance cholangiopancreatography: normal values and short-term effects of pancreatic duct drainage procedures in chronic pancreatitis. Initial results. Eur. Radiol. 15, 2110–2121 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. 47

    Calculli, L. et al. Exocrine pancreatic function assessed by secretin cholangio-Wirsung magnetic resonance imaging. Hepatobiliary Pancreat. Dis. Int. 7, 192–195 (2008).

    PubMed  Google Scholar 

  48. 48

    Bor, R., Madácsy, L., Fábián, A., Szepes, A. & Szepes, Z. Endoscopic retrograde pancreatography: when should we do it? World J. Gastrointest. Endosc. 7, 1023–1031 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49

    Zuccaro, G. & Sivak, M. V. Endoscopic ultrasonography in the diagnosis of chronic pancreatitis. Endoscopy 24 (Suppl. 1), 347–349 (1992).

    Article  PubMed  Google Scholar 

  50. 50

    Catalano, M. F. et al. EUS-based criteria for the diagnosis of chronic pancreatitis: the Rosemont classification. Gastrointest. Endosc. 69, 1251–1261 (2009).

    Article  PubMed  Google Scholar 

  51. 51

    Gardner, T. B. & Levy, M. J. EUS diagnosis of chronic pancreatitis. Gastrointest. Endosc. 71, 1280–1289 (2010).

    Article  PubMed  Google Scholar 

  52. 52

    Azemoto, N. et al. Utility of contrast-enhanced transabdominal ultrasonography to diagnose early chronic pancreatitis. Biomed. Res. Int. 2015, 393124 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  53. 53

    Iglesias-Garcia, J., Lariño-Noia, J., Abdulkader, I., Forteza, J. & Dominguez-Muñoz, J. E. Quantitative endoscopic ultrasound elastography: an accurate method for the differentiation of solid pancreatic masses. Gastroenterology 139, 1172–1180 (2010).

    Article  PubMed  Google Scholar 

  54. 54

    Iglesias-Garcia, J., Dominguez-Muñoz, J. E., Castiñeira-Alvariño, M., Luaces Regueira, M. & Lariño-Noia, J. Quantitative elastography associated with endoscopic ultrasound for the diagnosis of chronic pancreatitis. Endoscopy 45, 781–788 (2013).

    Article  PubMed  Google Scholar 

  55. 55

    Kongkam, P. et al. Combination of EUS-FNA and elastography (strain ratio) to exclude malignant solid pancreatic lesions: a prospective single-blinded study. J. Gastroenterol. Hepatol. 30, 1683–1689 (2015).

    Article  PubMed  Google Scholar 

  56. 56

    de Jong, K. et al. High prevalence of pancreatic cysts detected by screening magnetic resonance imaging examinations. Clin. Gastroenterol. Hepatol. 8, 806–811 (2010).

    Article  PubMed  Google Scholar 

  57. 57

    Laffan, T. A. et al. Prevalence of unsuspected pancreatic cysts on MDCT. AJR Am. J. Roentgenol. 191, 802–807 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  58. 58

    Brugge, W. R., Lauwers, G. Y., Sahani, D., Fernández-del, C. C. & Warshaw, A. L. Cystic neoplasms of the pancreas. N. Engl. J. Med. 351, 1218–1226 (2004).

    Article  CAS  PubMed  Google Scholar 

  59. 59

    de Jong, K., Bruno, M. J. & Fockens, P. Epidemiology, diagnosis, and management of cystic lesions of the pancreas. Gastroenterol. Res. Pract. 2012, 147465 (2012).

    Article  PubMed  Google Scholar 

  60. 60

    Grützmann, R., Niedergethmann, M., Pilarsky, C., Klöppel, G. & Saeger, H. D. Intraductal papillary mucinous tumors of the pancreas: biology, diagnosis, and treatment. Oncologist 15, 1294–1309 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  61. 61

    Adimoolam, V. et al. Endoscopic ultrasound identifies synchronous pancreas cystic lesions not seen on initial cross-sectional imaging. Pancreas 40, 1070–1072 (2011).

    Article  PubMed  Google Scholar 

  62. 62

    Anand, N., Sampath, K. & Wu, B. U. Cyst features and risk of malignancy in intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis. Clin. Gastroenterol. Hepatol. 11, 913–921; quiz e59–e60 (2013).

    Article  PubMed  Google Scholar 

  63. 63

    D'Onofrio, M. et al. Pancreatic multicenter ultrasound study (PAMUS). Eur. J. Radiol. 81, 630–638 (2012).

    Article  PubMed  Google Scholar 

  64. 64

    Beyer-Enke, S. A., Hocke, M., Ignee, A., Braden, B. & Dietrich, C. F. Contrast enhanced transabdominal ultrasound in the characterisation of pancreatic lesions with cystic appearance. JOP 11, 427–433 (2010).

    PubMed  Google Scholar 

  65. 65

    D'Onofrio, M. et al. Comparison of contrast-enhanced sonography and MRI in displaying anatomic features of cystic pancreatic masses. AJR Am. J. Roentgenol. 189, 1435–1442 (2007).

    Article  PubMed  Google Scholar 

  66. 66

    Hocke, M., Cui, X.-W., Domagk, D., Ignee, A. & Dietrich, C. F. Pancreatic cystic lesions: the value of contrast-enhanced endoscopic ultrasound to influence the clinical pathway. Endosc. Ultrasound 3, 123–130 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  67. 67

    Giovannini, M. et al. Results of a phase I-II study on intraductal confocal microscopy (IDCM) in patients with common bile duct (CBD) stenosis. Surg. Endosc. 25, 2247–2253 (2011).

    Article  CAS  PubMed  Google Scholar 

  68. 68

    Sultana, A. et al. What is the best way to identify malignant transformation within pancreatic IPMN: a systematic review and meta-analyses. Clin. Transl. Gastroenterol. 6, e130 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. 69

    Kim, S.-L. et al. The effect of PPAR-γ agonist on 18F-FDG uptake in tumor and macrophages and tumor cells. Nucl. Med. Biol. 36, 427–433 (2009).

    Article  CAS  PubMed  Google Scholar 

  70. 70

    Cornish, T. C. & Hruban, R. H. Pancreatic intraepithelial neoplasia. Surg. Pathol. Clin. 4, 523–535 (2011).

    Article  PubMed  Google Scholar 

  71. 71

    Jemal, A., Siegel, R., Xu, J. & Ward, E. Cancer statistics, 2010. CA Cancer J. Clin. 60, 277–300 (2010).

    Article  PubMed  Google Scholar 

  72. 72

    Allen, P. J. & Brennan, M. F. A. Selective approach to resection of cystic lesions of the pancreas: results from 539 consecutive patients. Ann. Surg. 245, 825–826 (2007).

    Article  PubMed Central  Google Scholar 

  73. 73

    Pancreatic Cancer Action Network. Pancreatic Cancer Facts 2016 [online], (2016).

  74. 74

    Rahib, L. et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74, 2913–2921 (2014).

    Article  CAS  PubMed  Google Scholar 

  75. 75

    National Cancer Institute SEER stat fact sheets: pancreatic cancer. (2015).

  76. 76

    Al-Hawary, M. M., Francis, I. R. & Anderson, M. A. Pancreatic solid and cystic neoplasms: diagnostic evaluation and intervention. Radiol. Clin. North Am. 53, 1037–1048 (2015).

    Article  PubMed  Google Scholar 

  77. 77

    Valls, C. et al. Dual-phase helical CT of pancreatic adenocarcinoma: assessment of resectability before surgery. AJR Am. J. Roentgenol. 178, 821–826 (2002).

    Article  PubMed  Google Scholar 

  78. 78

    Lee, E. S. & Lee, J. M. Imaging diagnosis of pancreatic cancer: a state-of-the-art review. World J. Gastroenterol. 20, 7864–7877 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  79. 79

    Bronstein, Y. L. et al. Detection of small pancreatic tumors with multiphasic helical CT. AJR Am. J. Roentgenol. 182, 619–623 (2004).

    Article  PubMed  Google Scholar 

  80. 80

    Tsunoda, T. et al. Staging and treatment for patients with pancreatic cancer. How small is an early pancreatic cancer? J. Hepatobiliary Pancreat. Surg. 5, 128–132 (1998).

    Article  CAS  PubMed  Google Scholar 

  81. 81

    Sahani, D. V., Shah, Z. K., Catalano, O. A., Boland, G. W. & Brugge, W. R. Radiology of pancreatic adenocarcinoma: current status of imaging. J. Gastroenterol. Hepatol. 23, 23–33 (2008).

    Article  PubMed  Google Scholar 

  82. 82

    Harewood, G. C. & Wiersema, M. J. Endosonography-guided fine needle aspiration biopsy in the evaluation of pancreatic masses. Am. J. Gastroenterol. 97, 1386–1391 (2002).

    Article  PubMed  Google Scholar 

  83. 83

    Templeton, A. W. & Brentnall, T. A. Screening and surgical outcomes of familial pancreatic cancer. Surg. Clin. North Am. 93, 629–645 (2013).

    Article  PubMed  Google Scholar 

  84. 84

    Helmstaedter, L. & Riemann, J. F. Pancreatic cancer —EUS and early diagnosis. Langenbecks Arch. Surg. 393, 923–927 (2008).

    Article  PubMed  Google Scholar 

  85. 85

    Pietryga, J. A. & Morgan, D. E. Imaging preoperatively for pancreatic adenocarcinoma. J. Gastrointest. Oncol. 6, 343–357 (2015).

    PubMed  PubMed Central  Google Scholar 

  86. 86

    Hicklin, D. J. & Ellis, L. M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol. 23, 1011–1027 (2005).

    Article  CAS  PubMed  Google Scholar 

  87. 87

    Longo, R., Cacciamani, F., Naso, G. & Gasparini, G. Pancreatic cancer: from molecular signature to target therapy. Crit. Rev. Oncol. Hematol. 68, 197–211 (2008).

    Article  CAS  PubMed  Google Scholar 

  88. 88

    Korc, M. Pathways for aberrant angiogenesis in pancreatic cancer. Mol. Cancer 2, 8 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. 89

    Tonra, J. R. et al. Synergistic antitumor effects of combined epidermal growth factor receptor and vascular endothelial growth factor receptor-2 targeted therapy. Clin. Cancer Res. 12, 2197–2207 (2006).

    Article  CAS  PubMed  Google Scholar 

  90. 90

    Spano, J.-P. et al. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study. Lancet 371, 2101–2108 (2008).

    Article  CAS  PubMed  Google Scholar 

  91. 91

    Itakura, J. et al. Enhanced expression of vascular endothelial growth factor in human pancreatic cancer correlates with local disease progression. Clin. Cancer Res. 3, 1309–1316 (1997).

    CAS  PubMed  Google Scholar 

  92. 92

    Büchler, P. et al. Target therapy using a small molecule inhibitor against angiogenic receptors in pancreatic cancer. Neoplasia 9, 119–127 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. 93

    Higgins, K. J., Abdelrahim, M., Liu, S., Yoon, K. & Safe, S. Regulation of vascular endothelial growth factor receptor-2 expression in pancreatic cancer cells by Sp proteins. Biochem. Biophys. Res. Commun. 345, 292–301 (2006).

    Article  CAS  PubMed  Google Scholar 

  94. 94

    Luo, J. et al. Pancreatic cancer cell-derived vascular endothelial growth factor is biologically active in vitro and enhances tumorigenicity in vivo. Int. J. Cancer 92, 361–369 (2001).

    Article  CAS  PubMed  Google Scholar 

  95. 95

    Shi, Q. et al. Constitutive Sp1 activity is essential for differential constitutive expression of vascular endothelial growth factor in human pancreatic adenocarcinoma. Cancer Res. 61, 4143–4154 (2001).

    CAS  PubMed  Google Scholar 

  96. 96

    Korpanty, G., Carbon, J. G., Grayburn, P. A., Fleming, J. B. & Brekken, R. A. Monitoring response to anticancer therapy by targeting microbubbles to tumor vasculature. Clin. Cancer Res. 13, 323–330 (2007).

    Article  CAS  PubMed  Google Scholar 

  97. 97

    Deshpande, N., Ren, Y., Foygel, K., Rosenberg, J. & Willmann, J. K. Tumor angiogenic marker expression levels during tumor growth: longitudinal assessment with molecularly targeted microbubbles and US imaging. Radiology 258, 804–811 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  98. 98

    Pysz, M. A. et al. Vascular endothelial growth factor receptor type 2-targeted contrast-enhanced US of pancreatic cancer neovasculature in a genetically engineered mouse model: potential for earlier detection. Radiology 274, 790–799 (2015).

    Article  PubMed  Google Scholar 

  99. 99

    Quail, D. F. & Joyce, J. A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19, 1423–1437 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. 100

    Drifka, C. R. et al. Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis. Mod. Pathol. 28, 1470–1480 (2015).

    Article  CAS  PubMed  Google Scholar 

  101. 101

    Ouban, A., Muraca, P., Yeatman, T. & Coppola, D. Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas. Hum. Pathol. 34, 803–808 (2003).

    Article  CAS  PubMed  Google Scholar 

  102. 102

    Zhou, H. et al. IGF1 receptor targeted theranostic nanoparticles for targeted and image-guided therapy of pancreatic cancer. ACS Nano 9, 7976–7991 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. 103

    Thomas, S. et al. Development of secreted protein and acidic and rich in cysteine (SPARC) targeted nanoparticles for the prognostic molecular imaging of metastatic prostate cancer. J. Nanomed. Nanotechnol. 2, (2011).

  104. 104

    Neuzillet, C. et al. Stromal expression of SPARC in pancreatic adenocarcinoma. Cancer Metastasis Rev. 32, 585–602 (2013).

    Article  CAS  PubMed  Google Scholar 

  105. 105

    Kelly, K. A. et al. Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma. PLoS Med. 5, e85 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. 106

    Shin, S. J. et al. Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer. Proc. Natl Acad. Sci. USA 110, 19414–19419 (2013).

    Article  CAS  PubMed  Google Scholar 

  107. 107

    Bausch, D. et al. Plectin-1 as a novel biomarker for pancreatic cancer. Clin. Cancer Res. 17, 302–309 (2011).

    Article  CAS  PubMed  Google Scholar 

  108. 108

    US National Library of Medicine., (2013).

  109. 109

    Kannagi, R., Izawa, M., Koike, T., Miyazaki, K. & Kimura, N. Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci. 95, 377–384 (2004).

    Article  CAS  PubMed  Google Scholar 

  110. 110

    Dimastromatteo, J., Houghton, J. L., Lewis, J. S. & Kelly, K. A. Challenges of pancreatic cancer. Cancer J. 21, 188–193 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. 111

    Viola-Villegas, N. T. et al. Applying PET to broaden the diagnostic utility of the clinically validated CA19.9 serum biomarker for oncology. J. Nucl. Med. 54, 1876–1882 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. 112

    Houghton, J. L. et al. Site-specifically labeled CA19.9-targeted immunoconjugates for the PET, NIRF, and multimodal PET/NIRF imaging of pancreatic cancer. Proc. Natl Acad. Sci. USA 112, 15850–15855 (2015).

    Article  CAS  PubMed  Google Scholar 

  113. 113

    Bünger, S., Laubert, T., Roblick, U. J. & Habermann, J. K. Serum biomarkers for improved diagnostic of pancreatic cancer: a current overview. J. Cancer Res. Clin. Oncol. 137, 375–389 (2011).

    Article  CAS  PubMed  Google Scholar 

  114. 114

    Boonstra, M. C. et al. Preclinical evaluation of a novel CEA-targeting near-infrared fluorescent tracer delineating colorectal and pancreatic tumors. Int. J. Cancer 137, 1910–1920 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. 115

    Jiang, T. et al. Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proc. Natl Acad. Sci. USA 101, 17867–17872 (2004).

    Article  CAS  PubMed  Google Scholar 

  116. 116

    Nguyen, Q. T. et al. Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival. Proc. Natl Acad. Sci. USA 107, 4317–4322 (2010).

    Article  CAS  PubMed  Google Scholar 

  117. 117

    Metildi, C. A. et al. Ratiometric activatable cell-penetrating peptides label pancreatic cancer, enabling fluorescence-guided surgery, which reduces metastases and recurrence in orthotopic mouse models. Ann. Surg. Oncol. 22, 2082–2087 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  118. 118

    Pociot, F. & Lernmark, Å. Genetic risk factors for type 1 diabetes. Lancet 387, 2331–2339 (2016).

    Article  CAS  PubMed  Google Scholar 

  119. 119

    Ribaric, S. The rationale for insulin therapy in Alzheimer's disease. Molecules 21, E689 (2016).

    Article  CAS  PubMed  Google Scholar 

  120. 120

    de la Monte, S. M. & Wands, J. R. Alzheimer's disease is type 3 diabetes-evidence reviewed. J. Diabetes Sci. Technol. 2, 1101–1113 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  121. 121

    Diabetes Atlas (2016).

  122. 122

    Kim, D. L., Kim, S. D., Kim, S. K., Park, S. & Song, K. H. Is an oral glucose tolerance test still valid for diagnosing diabetes mellitus? Diabetes Metab. J. 40, 118–128 (2016).

    Article  PubMed  Google Scholar 

  123. 123

    Rahier, J., Guiot, Y., Goebbels, R. M., Sempoux, C. & Henquin, J. C. Pancreatic β-cell mass in European subjects with type 2 diabetes. Diabetes Obes. Metab. 10, 32–42 (2008).

    Article  PubMed  Google Scholar 

  124. 124

    Perry, T. & Greig, N. H. The glucagon-like peptides: a double-edged therapeutic sword? Trends Pharmacol. Sci. 24, 377–383 (2003).

    Article  CAS  PubMed  Google Scholar 

  125. 125

    Reiner, T. et al. Accurate measurement of pancreatic islet β-cell mass using a second-generation fluorescent exendin-4 analog. Proc. Natl Acad. Sci. USA 108, 12815–12820 (2011).

    Article  PubMed  Google Scholar 

  126. 126

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

    CAS  PubMed  Google Scholar 

  127. 127

    Wicki, A. et al. [Lys40(Ahx-DTPA-111In)NH2]-exendin-4 is a highly efficient radiotherapeutic for glucagon-like peptide-1 receptor-targeted therapy for insulinoma. Clin. Cancer Res. 13, 3696–3705 (2007).

    Article  CAS  PubMed  Google Scholar 

  128. 128

    Wu, Z. et al. In vivo imaging of transplanted islets with 64Cu-DO3A-VS-Cys40-Exendin-4 by targeting GLP-1 receptor. Bioconjug. Chem. 22, 1587–1594 (2011).

    Article  CAS  PubMed  Google Scholar 

  129. 129

    Connolly, B. M. et al. Ex vivo imaging of pancreatic β cells using a radiolabeled GLP-1 receptor agonist. Mol. Imaging Biol. 14, 79–87 (2012).

    Article  PubMed  Google Scholar 

  130. 130

    Brand, C. et al. In vivo imaging of GLP-1R with a targeted bimodal PET/fluorescence imaging agent. Bioconjug. Chem. 25, 1323–1330 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. 131

    Behnam Azad, B. et al. Synthesis and evaluation of optical and PET GLP-1 peptide analogues for GLP-1R imaging. Mol. Imaging 14, 1–16 (2015).

    Article  CAS  Google Scholar 

  132. 132

    Henquin, J.-C., Nenquin, M., Stiernet, P. & Ahren, B. In vivo and in vitro glucose-induced biphasic insulin secretion in the mouse: pattern and role of cytoplasmic Ca2+ and amplification signals in β-cells. Diabetes 55, 441–451 (2006).

    Article  CAS  PubMed  Google Scholar 

  133. 133

    Antkowiak, P. F. et al. Noninvasive assessment of pancreatic β-cell function in vivo with manganese-enhanced magnetic resonance imaging. Am. J. Physiol. Endocrinol. Metab. 296, E573–E578 (2009).

    Article  CAS  PubMed  Google Scholar 

  134. 134

    Antkowiak, P. F., Stevens, B. K., Nunemaker, C. S., McDuffie, M. & Epstein, F. H. Manganese-enhanced magnetic resonance imaging detects declining pancreatic β-cell mass in a cyclophosphamide-accelerated mouse model of type 1 diabetes. Diabetes 62, 44–48 (2013).

    Article  CAS  PubMed  Google Scholar 

  135. 135

    Ablamunits, V., Quintana, F., Reshef, T., Elias, D. & Cohen, I. R. Acceleration of autoimmune diabetes by cyclophosphamide is associated with an enhanced IFN-γ secretion pathway. J. Autoimmun. 13, 383–392 (1999).

    Article  CAS  PubMed  Google Scholar 

  136. 136

    Lubag, A. J. M., De Leon-Rodriguez, L. M., Burgess, S. C. & Sherry, A. D. Noninvasive MRI of β-cell function using a Zn2+-responsive contrast agent. Proc. Natl Acad. Sci. USA 108, 18400–18405 (2011).

    Article  PubMed  Google Scholar 

Download references


The authors thank S. L. Hasbrouck, Curry School of Education, University of Virginia, for her kind help reading and editing the manuscript.

Author information




All authors contributed equally to the article.

Corresponding author

Correspondence to Kimberly A. Kelly.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dimastromatteo, J., Brentnall, T. & Kelly, K. Imaging in pancreatic disease. Nat Rev Gastroenterol Hepatol 14, 97–109 (2017).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing