Molecular imaging of pancreatic neoplasms

Abstract

Purpose

Pancreatic ductal adenocarcinomas (PDACs) derive from the exocrine pancreas and account for the majority of pancreatic tumors (95%). It is the seventh leading cause of cancer-related deaths and shows one of the worst prognoses in oncology with a 5-year survival rate of 9%. Pancreatic neuroendocrine tumors (pNETs) derive from the endocrine part of the pancreas. Well-differentiated pNETs are characterized by slow tumor growth and good life expectancy. In all pancreatic tumor entities, imaging plays a key role. Hybrid imaging modalities (PET/CT and PET/MRI) combine functional and structural data and may reflect a more accurate assessment of disease spread which directs subsequent treatment planning and patient management.

Methods

A comprehensive search strategy was used based on PubMed and SCOPUS databases from 1999 to date.

Results

FDG PET/CT in PDAC shows high sensitivity and specificity in evaluation of T- and M-staging but lesser sensitivity of N-staging. In restaging, metabolic changes occur earlier than morphological changes in tumor size and can be assessed by molecular imaging which can act as a predictor of prognosis. 68Ga-labeled somatostatin analogs (SSAs) are the gold standard in imaging of well-differentiated pNETs. In poorly differentiated pNETs, FDG is the radiotracer of choice. PET/MRI may have added value due to higher soft-tissue contrast. However, more prospective studies comparing PET/CT and PET/MRI systems are needed.

Conclusion

FDG PET/CT plays a key role in PDAC in staging, restaging as well as disease monitoring during follow-up. Functional imaging with 68Ga-labeled SSA is the gold standard in imaging of well-differentiated pNETs.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

Availability of data and material (data transparency)

This is a review article and all reviewed studies are referenced.

References

  1. 1.

    Siegel RL, Miller KD, Jemal A (2020) Cancer statistics, 2020. CA Cancer J Clin 70(1):7–30. https://doi.org/10.3322/caac.21590

    Article  Google Scholar 

  2. 2.

    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492

    Article  Google Scholar 

  3. 3.

    Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69(1):7–34. https://doi.org/10.3322/caac.21551

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74(11):2913–2921. https://doi.org/10.1158/0008-5472.CAN-14-0155

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Philip PA, Mooney M, Jaffe D, Eckhardt G, Moore M, Meropol N, Emens L, O’Reilly E, Korc M, Ellis L, Benedetti J, Rothenberg M, Willett C, Tempero M, Lowy A, Abbruzzese J, Simeone D, Hingorani S, Berlin J, Tepper J (2009) Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment. J Clin Oncol 27(33):5660–5669. https://doi.org/10.1200/JCO.2009.21.9022

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Katz MH, Savides TJ, Moossa AR, Bouvet M (2005) An evidence-based approach to the diagnosis and staging of pancreatic cancer. Pancreatology 5(6):576–590. https://doi.org/10.1159/000087500

    Article  PubMed  Google Scholar 

  7. 7.

    Duan H, Baratto L, Iagaru A (2019) The Role of PET/CT in the Imaging of Pancreatic Neoplasms. Semin Ultrasound CT MR 40(6):500–508. https://doi.org/10.1053/j.sult.2019.04.006

    Article  PubMed  Google Scholar 

  8. 8.

    Lopez NE, Prendergast C, Lowy AM (2014) Borderline resectable pancreatic cancer: definitions and management. World J Gastroenterol 20(31):10740–10751. https://doi.org/10.3748/wjg.v20.i31.10740

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW (2004) Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg 91(5):586–594. https://doi.org/10.1002/bjs.4484

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Soriano A, Castells A, Ayuso C, Ayuso JR, de Caralt MT, Gines MA, Real MI, Gilabert R, Quinto L, Trilla A, Feu F, Montanya X, Fernandez-Cruz L, Navarro S (2004) Preoperative staging and tumor resectability assessment of pancreatic cancer: prospective study comparing endoscopic ultrasonography, helical computed tomography, magnetic resonance imaging, and angiography. Am J Gastroenterol 99(3):492–501. https://doi.org/10.1111/j.1572-0241.2004.04087.x

    Article  PubMed  Google Scholar 

  11. 11.

    Warburg O (1956) On the origin of cancer cells. Science 123(3191):309–314

    CAS  Article  Google Scholar 

  12. 12.

    Wang Y, Chiu E, Rosenberg J, Gambhir SS (2007) Standardized uptake value atlas: characterization of physiological 2-deoxy-2-[18F]fluoro-d-glucose uptake in normal tissues. Mol Imaging Biol 9(2):83–90. https://doi.org/10.1007/s11307-006-0075-y

    Article  PubMed  Google Scholar 

  13. 13.

    Shan T, Chen S, Chen X, Lin WR, Li W, Ma J, Wu T, Cui X, Ji H, Li Y, Kang Y (2017) Cancer-associated fibroblasts enhance pancreatic cancer cell invasion by remodeling the metabolic conversion mechanism. Oncol Rep 37(4):1971–1979. https://doi.org/10.3892/or.2017.5479

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Ye H, Zhou Q, Zheng S, Li G, Lin Q, Wei L, Fu Z, Zhang B, Liu Y, Li Z, Chen R (2018) Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma. Cell Death Dis 9(5):453. https://doi.org/10.1038/s41419-018-0486-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Chaika NV, Yu F, Purohit V, Mehla K, Lazenby AJ, DiMaio D, Anderson JM, Yeh JJ, Johnson KR, Hollingsworth MA, Singh PK (2012) Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma. PLoS ONE 7(3):e32996. https://doi.org/10.1371/journal.pone.0032996

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Chikamoto A, Inoue R, Komohara Y, Sakamaki K, Hashimoto D, Shiraishi S, Takamori H, Yamashita YI, Yoshida N, Yamanaka T, Yamashita Y, Baba H (2017) Preoperative high maximum standardized uptake value in association with glucose transporter 1 predicts poor prognosis in pancreatic cancer. Ann Surg Oncol 24(7):2040–2046. https://doi.org/10.1245/s10434-017-5799-1

    Article  PubMed  Google Scholar 

  17. 17.

    Yeo CJ, Cameron JL, Sohn TA, Lillemoe KD, Pitt HA, Talamini MA, Hruban RH, Ord SE, Sauter PK, Coleman J, Zahurak ML, Grochow LB, Abrams RA (1997) Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg 226(3):248–257 (discussion 257–260)

    CAS  Article  Google Scholar 

  18. 18.

    DeWitt J, Devereaux B, Chriswell M, McGreevy K, Howard T, Imperiale TF, Ciaccia D, Lane KA, Maglinte D, Kopecky K, LeBlanc J, McHenry L, Madura J, Aisen A, Cramer H, Cummings O, Sherman S (2004) Comparison of endoscopic ultrasonography and multidetector computed tomography for detecting and staging pancreatic cancer. Ann Intern Med 141(10):753–763

    Article  Google Scholar 

  19. 19.

    Zhang J, Zuo CJ, Jia NY, Wang JH, Hu SP, Yu ZF, Zheng Y, Zhang AY, Feng XY (2015) Cross-modality PET/CT and contrast-enhanced CT imaging for pancreatic cancer. World J Gastroenterol 21(10):2988–2996. https://doi.org/10.3748/wjg.v21.i10.2988

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Buchs NC, Buhler L, Bucher P, Willi JP, Frossard JL, Roth AD, Addeo P, Rosset A, Terraz S, Becker CD, Ratib O, Morel P (2011) Value of contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography in detection and presurgical assessment of pancreatic cancer: a prospective study. J Gastroenterol Hepatol 26(4):657–662. https://doi.org/10.1111/j.1440-1746.2010.06525.x

    Article  PubMed  Google Scholar 

  21. 21.

    Bang S, Chung HW, Park SW, Chung JB, Yun M, Lee JD, Song SY (2006) The clinical usefulness of 18-fluorodeoxyglucose positron emission tomography in the differential diagnosis, staging, and response evaluation after concurrent chemoradiotherapy for pancreatic cancer. J Clin Gastroenterol 40(10):923–929. https://doi.org/10.1097/01.mcg.0000225672.68852.05

    Article  PubMed  Google Scholar 

  22. 22.

    Gambhir SS, Czernin J, Schwimmer J, Silverman DH, Coleman RE, Phelps ME (2001) A tabulated summary of the FDG PET literature. J Nucl Med 42(5 Suppl):1S-93S

    CAS  PubMed  Google Scholar 

  23. 23.

    Rose DM, Delbeke D, Beauchamp RD, Chapman WC, Sandler MP, Sharp KW, Richards WO, Wright JK, Frexes ME, Pinson CW, Leach SD (1999) 18Fluorodeoxyglucose-positron emission tomography in the management of patients with suspected pancreatic cancer. Ann Surg 229(5):729–737 (discussion 737–728)

    CAS  Article  Google Scholar 

  24. 24.

    Lemke AJ, Niehues SM, Hosten N, Amthauer H, Boehmig M, Stroszczynski C, Rohlfing T, Rosewicz S, Felix R (2004) Retrospective digital image fusion of multidetector CT and 18F-FDG PET: clinical value in pancreatic lesions–a prospective study with 104 patients. J Nucl Med 45(8):1279–1286

    PubMed  Google Scholar 

  25. 25.

    Santhosh S, Mittal BR, Bhasin D, Srinivasan R, Rana S, Das A, Nada R, Bhattacharya A, Gupta R, Kapoor R (2013) Role of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in the characterization of pancreatic masses: experience from tropics. J Gastroenterol Hepatol 28(2):255–261. https://doi.org/10.1111/jgh.12068

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Tang S, Huang G, Liu J, Liu T, Treven L, Song S, Zhang C, Pan L, Zhang T (2011) Usefulness of 18F-FDG PET, combined FDG-PET/CT and EUS in diagnosing primary pancreatic carcinoma: a meta-analysis. Eur J Radiol 78(1):142–150. https://doi.org/10.1016/j.ejrad.2009.09.026

    Article  PubMed  Google Scholar 

  27. 27.

    Zimny M, Bares R, Fass J, Adam G, Cremerius U, Dohmen B, Klever P, Sabri O, Schumpelick V, Buell U (1997) Fluorine-18 fluorodeoxyglucose positron emission tomography in the differential diagnosis of pancreatic carcinoma: a report of 106 cases. Eur J Nucl Med 24(6):678–682

    CAS  PubMed  Google Scholar 

  28. 28.

    Kauhanen SP, Komar G, Seppanen MP, Dean KI, Minn HR, Kajander SA, Rinta-Kiikka I, Alanen K, Borra RJ, Puolakkainen PA, Nuutila P, Ovaska JT (2009) A prospective diagnostic accuracy study of 18F-fluorodeoxyglucose positron emission tomography/computed tomography, multidetector row computed tomography, and magnetic resonance imaging in primary diagnosis and staging of pancreatic cancer. Ann Surg 250(6):957–963. https://doi.org/10.1097/SLA.0b013e3181b2fafa

    Article  PubMed  Google Scholar 

  29. 29.

    Wang XY, Yang F, Jin C, Fu DL (2014) Utility of PET/CT in diagnosis, staging, assessment of resectability and metabolic response of pancreatic cancer. World J Gastroenterol 20(42):15580–15589. https://doi.org/10.3748/wjg.v20.i42.15580

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Wang L, Dong P, Wang WG, Tian BL (2017) Positron emission tomography modalities prevent futile radical resection of pancreatic cancer: a meta-analysis. Int J Surg 46:119–125. https://doi.org/10.1016/j.ijsu.2017.09.003

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Asagi A, Ohta K, Nasu J, Tanada M, Nadano S, Nishimura R, Teramoto N, Yamamoto K, Inoue T, Iguchi H (2013) Utility of contrast-enhanced FDG-PET/CT in the clinical management of pancreatic cancer: impact on diagnosis, staging, evaluation of treatment response, and detection of recurrence. Pancreas 42(1):11–19. https://doi.org/10.1097/MPA.0b013e3182550d77

    Article  PubMed  Google Scholar 

  32. 32.

    Strobel K, Heinrich S, Bhure U, Soyka J, Veit-Haibach P, Pestalozzi BC, Clavien PA, Hany TF (2008) Contrast-enhanced 18F-FDG PET/CT: 1-stop-shop imaging for assessing the resectability of pancreatic cancer. J Nucl Med 49(9):1408–1413. https://doi.org/10.2967/jnumed.108.051466

    Article  PubMed  Google Scholar 

  33. 33.

    Chang JS, Choi SH, Lee Y, Kim KH, Park JY, Song SY, Cho A, Yun M, Lee JD, Seong J (2014) Clinical usefulness of (1)(8)F-fluorodeoxyglucose-positron emission tomography in patients with locally advanced pancreatic cancer planned to undergo concurrent chemoradiation therapy. Int J Radiat Oncol Biol Phys 90(1):126–133. https://doi.org/10.1016/j.ijrobp.2014.05.030

    Article  PubMed  Google Scholar 

  34. 34.

    Barber TW, Kalff V, Cherk MH, Yap KS, Evans P, Kelly MJ (2011) 18 F-FDG PET/CT influences management in patients with known or suspected pancreatic cancer. Intern Med J 41(11):776–783. https://doi.org/10.1111/j.1445-5994.2010.02257.x

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Santhosh S, Mittal BR, Bhasin DK, Rana SS, Gupta R, Das A, Nada R (2017) Fluorodeoxyglucose-positron emission tomography/computed tomography performs better than contrast-enhanced computed tomography for metastasis evaluation in the initial staging of pancreatic adenocarcinoma. Ann Nucl Med 31(8):575–581. https://doi.org/10.1007/s12149-017-1193-0

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Diederichs CG, Staib L, Vogel J, Glasbrenner B, Glatting G, Brambs HJ, Beger HG, Reske SN (2000) Values and limitations of 18F-fluorodeoxyglucose-positron-emission tomography with preoperative evaluation of patients with pancreatic masses. Pancreas 20(2):109–116

    CAS  Article  Google Scholar 

  37. 37.

    Donswijk ML, Hess S, Mulders T, Lam MG (2014) [18F]Fluorodeoxyglucose PET/computed tomography in gastrointestinal malignancies. PET Clin 9(4):421–441v–vi. https://doi.org/10.1016/j.cpet.2014.07.001

    Article  PubMed  Google Scholar 

  38. 38.

    Higashi T, Saga T, Nakamoto Y, Ishimori T, Fujimoto K, Doi R, Imamura M, Konishi J (2003) Diagnosis of pancreatic cancer using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET)—usefulness and limitations in “clinical reality.” Ann Nucl Med 17(4):261–279

    Article  Google Scholar 

  39. 39.

    Yoshioka M, Sato T, Furuya T, Shibata S, Andoh H, Asanuma Y, Hatazawa J, Shimosegawa E, Koyama K, Yamamoto Y (2004) Role of positron emission tomography with 2-deoxy-2-[18F]fluoro-d-glucose in evaluating the effects of arterial infusion chemotherapy and radiotherapy on pancreatic cancer. J Gastroenterol 39(1):50–55. https://doi.org/10.1007/s00535-003-1244-2

    Article  PubMed  Google Scholar 

  40. 40.

    Ruf J, Lopez Hanninen E, Oettle H, Plotkin M, Pelzer U, Stroszczynski C, Felix R, Amthauer H (2005) Detection of recurrent pancreatic cancer: comparison of FDG-PET with CT/MRI. Pancreatology 5(2–3):266–272. https://doi.org/10.1159/000085281

    Article  PubMed  Google Scholar 

  41. 41.

    Heinrich S, Goerres GW, Schafer M, Sagmeister M, Bauerfeind P, Pestalozzi BC, Hany TF, von Schulthess GK, Clavien PA (2005) Positron emission tomography/computed tomography influences on the management of resectable pancreatic cancer and its cost-effectiveness. Ann Surg 242(2):235–243

    Article  Google Scholar 

  42. 42.

    Matsumoto I, Shirakawa S, Shinzeki M, Asari S, Goto T, Ajiki T, Fukumoto T, Kitajima K, Ku Y (2013) 18-Fluorodeoxyglucose positron emission tomography does not aid in diagnosis of pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol 11(6):712–718. https://doi.org/10.1016/j.cgh.2012.12.033

    Article  PubMed  Google Scholar 

  43. 43.

    Strobel O, Buchler MW (2013) Pancreatic cancer: FDG-PET is not useful in early pancreatic cancer diagnosis. Nat Rev Gastroenterol Hepatol 10(4):203–205. https://doi.org/10.1038/nrgastro.2013.42

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Cong L, Liu Q, Zhang R, Cui M, Zhang X, Gao X, Guo J, Dai M, Zhang T, Liao Q, Zhao Y (2018) Tumor size classification of the 8(th) edition of TNM staging system is superior to that of the 7(th) edition in predicting the survival outcome of pancreatic cancer patients after radical resection and adjuvant chemotherapy. Sci Rep 8(1):10383. https://doi.org/10.1038/s41598-018-28193-4

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Sahani DV, Bonaffini PA, Catalano OA, Guimaraes AR, Blake MA (2012) State-of-the-art PET/CT of the pancreas: current role and emerging indications. Radiographics 32(4):1133–1158. https://doi.org/10.1148/rg.324115143 (discussion 1158–1160)

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Maemura K, Takao S, Shinchi H, Noma H, Mataki Y, Kurahara H, Jinnouchi S, Aikou T (2006) Role of positron emission tomography in decisions on treatment strategies for pancreatic cancer. J Hepatobiliary Pancreat Surg 13(5):435–441. https://doi.org/10.1007/s00534-006-1102-8

    Article  PubMed  Google Scholar 

  47. 47.

    Sperti C, Pasquali C, Bissoli S, Chierichetti F, Liessi G, Pedrazzoli S (2010) Tumor relapse after pancreatic cancer resection is detected earlier by 18-FDG PET than by CT. J Gastrointest Surg 14(1):131–140. https://doi.org/10.1007/s11605-009-1010-8

    Article  PubMed  Google Scholar 

  48. 48.

    Seufferlein T, Bachet JB, Van Cutsem E, Rougier P, Group EGW (2012) Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):vii33-40. https://doi.org/10.1093/annonc/mds224

    Article  PubMed  Google Scholar 

  49. 49.

    Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goere D, Seufferlein T, Haustermans K, Van Laethem JL, Conroy T, Arnold D, Committee EG (2015) Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(Suppl 5):v56-68. https://doi.org/10.1093/annonc/mdv295

    Article  PubMed  Google Scholar 

  50. 50.

    Tempero MA (2019) NCCN guidelines updates: pancreatic cancer. J Natl Compr Canc Netw 17(5.5):603–605. https://doi.org/10.6004/jnccn.2019.5007

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Groot VP, Rezaee N, Wu W, Cameron JL, Fishman EK, Hruban RH, Weiss MJ, Zheng L, Wolfgang CL, He J (2018) Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg 267(5):936–945. https://doi.org/10.1097/SLA.0000000000002234

    Article  PubMed  Google Scholar 

  52. 52.

    Huicochea Castellanos S, Corrias G, Ulaner GA, Dunphy M, Junting Z, Capanu M, Balachandran V, Giancipoli RG, Monti S, Mannelli L (2019) Detection of recurrent pancreatic cancer: value of second-opinion interpretations of cross-sectional images by subspecialized radiologists. Abdom Radiol (NY) 44(2):586–592. https://doi.org/10.1007/s00261-018-1765-z

    Article  Google Scholar 

  53. 53.

    Kitajima K, Murakami K, Yamasaki E, Kaji Y, Shimoda M, Kubota K, Suganuma N, Sugimura K (2010) Performance of integrated FDG-PET/contrast-enhanced CT in the diagnosis of recurrent pancreatic cancer: comparison with integrated FDG-PET/non-contrast-enhanced CT and enhanced CT. Mol Imaging Biol 12(4):452–459. https://doi.org/10.1007/s11307-009-0271-7

    Article  PubMed  Google Scholar 

  54. 54.

    Daamen LA, Groot VP, Goense L, Wessels FJ, Borel Rinkes IH, Intven MPW, van Santvoort HC, Molenaar IQ (2018) The diagnostic performance of CT versus FDG PET-CT for the detection of recurrent pancreatic cancer: a systematic review and meta-analysis. Eur J Radiol 106:128–136. https://doi.org/10.1016/j.ejrad.2018.07.010

    Article  PubMed  Google Scholar 

  55. 55.

    Wahl RL, Jacene H, Kasamon Y, Lodge MA (2009) From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med 50(Suppl 1):122S-150S. https://doi.org/10.2967/jnumed.108.057307

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Schellenberg D, Quon A, Minn AY, Graves EE, Kunz P, Ford JM, Fisher GA, Goodman KA, Koong AC, Chang DT (2010) 18Fluorodeoxyglucose PET is prognostic of progression-free and overall survival in locally advanced pancreas cancer treated with stereotactic radiotherapy. Int J Radiat Oncol Biol Phys 77(5):1420–1425. https://doi.org/10.1016/j.ijrobp.2009.06.049

    Article  PubMed  Google Scholar 

  57. 57.

    Sperti C, Pasquali C, Chierichetti F, Ferronato A, Decet G, Pedrazzoli S (2003) 18-Fluorodeoxyglucose positron emission tomography in predicting survival of patients with pancreatic carcinoma. J Gastrointest Surg 7(8):953–959 (discussion 959–960)

    Article  Google Scholar 

  58. 58.

    Topkan E, Parlak C, Kotek A, Yapar AF, Pehlivan B (2011) Predictive value of metabolic 18FDG-PET response on outcomes in patients with locally advanced pancreatic carcinoma treated with definitive concurrent chemoradiotherapy. BMC Gastroenterol 11:123. https://doi.org/10.1186/1471-230X-11-123

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Kittaka H, Takahashi H, Ohigashi H, Gotoh K, Yamada T, Tomita Y, Hasegawa Y, Yano M, Ishikawa O (2013) Role of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in predicting the pathologic response to preoperative chemoradiation therapy in patients with resectable T3 pancreatic cancer. World J Surg 37(1):169–178. https://doi.org/10.1007/s00268-012-1775-x

    Article  PubMed  Google Scholar 

  60. 60.

    Barreto SG, Loveday B, Windsor JA, Pandanaboyana S (2019) Detecting tumour response and predicting resectability after neoadjuvant therapy for borderline resectable and locally advanced pancreatic cancer. ANZ J Surg 89(5):481–487. https://doi.org/10.1111/ans.14764

    Article  PubMed  Google Scholar 

  61. 61.

    Yoo SH, Kang SY, Cheon GJ, Oh DY, Bang YJ (2020) Predictive role of temporal changes in intratumoral metabolic heterogeneity during palliative chemotherapy in patients with advanced pancreatic cancer: a prospective cohort study. J Nucl Med 61(1):33–39. https://doi.org/10.2967/jnumed.119.226407

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Ford EC, Herman J, Yorke E, Wahl RL (2009) 18F-FDG PET/CT for image-guided and intensity-modulated radiotherapy. J Nucl Med 50(10):1655–1665. https://doi.org/10.2967/jnumed.108.055780

    Article  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Li XX, Liu NB, Zhu L, Yuan XK, Yang CW, Ren P, Gong LL, Zhao LJ, Xu WG, Wang P (2015) Consequences of additional use of contrast-enhanced (18)F-FDG PET/CT in target volume delineation and dose distribution for pancreatic cancer. Br J Radiol 88(1051):20140590. https://doi.org/10.1259/bjr.20140590

    Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Fiorentino A, Laudicella R, Ciurlia E, Annunziata S, Lancellotta V, Mapelli P, Tuscano C, Caobelli F, Evangelista L, Marino L, Quartuccio N, Fiore M, Borghetti P, Chiaravalloti A, Ricci M, Desideri I, Alongi P, Members AG-IAoRO-Y, Group AIAoNM-YMW (2019) Positron emission tomography with computed tomography imaging (PET/CT) for the radiotherapy planning definition of the biological target volume: PART 2. Crit Rev Oncol Hematol 139:117–124. https://doi.org/10.1016/j.critrevonc.2019.03.008

    Article  PubMed  Google Scholar 

  65. 65.

    Martin B, Paesmans M, Mascaux C, Berghmans T, Lothaire P, Meert AP, Lafitte JJ, Sculier JP (2004) Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. Br J Cancer 91(12):2018–2025. https://doi.org/10.1038/sj.bjc.6602233

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  66. 66.

    de Azambuja E, Cardoso F, de Castro JG, Colozza M, Mano MS, Durbecq V, Sotiriou C, Larsimont D, Piccart-Gebhart MJ, Paesmans M (2007) Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer 96(10):1504–1513. https://doi.org/10.1038/sj.bjc.6603756

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Herrmann K, Eckel F, Schmidt S, Scheidhauer K, Krause BJ, Kleeff J, Schuster T, Wester HJ, Friess H, Schmid RM, Schwaiger M, Buck AK (2008) In vivo characterization of proliferation for discriminating cancer from pancreatic pseudotumors. J Nucl Med 49(9):1437–1444. https://doi.org/10.2967/jnumed.108.052027

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    Herrmann K, Erkan M, Dobritz M, Schuster T, Siveke JT, Beer AJ, Wester HJ, Schmid RM, Friess H, Schwaiger M, Kleeff J, Buck AK (2012) Comparison of 3’-deoxy-3’-[(1)(8)F]fluorothymidine positron emission tomography (FLT PET) and FDG PET/CT for the detection and characterization of pancreatic tumours. Eur J Nucl Med Mol Imaging 39(5):846–851. https://doi.org/10.1007/s00259-012-2061-8

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Challapalli A, Barwick T, Pearson RA, Merchant S, Mauri F, Howell EC, Sumpter K, Maxwell RJ, Aboagye EO, Sharma R (2015) 3’-Deoxy-3’-(1)(8)F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer. Eur J Nucl Med Mol Imaging 42(6):831–840. https://doi.org/10.1007/s00259-015-3000-2

    CAS  Article  PubMed  Google Scholar 

  70. 70.

    Mittra ES, Koglin N, Mosci C, Kumar M, Hoehne A, Keu KV, Iagaru AH, Mueller A, Berndt M, Bullich S, Friebe M, Schmitt-Willich H, Gekeler V, Fels LM, Bacher-Stier C, Moon DH, Chin FT, Stephens AW, Dinkelborg LM, Gambhir SS (2016) Pilot preclinical and clinical evaluation of (4S)-4-(3-[18F]Fluoropropyl)-l-glutamate (18F-FSPG) for PET/CT imaging of intracranial malignancies. PLoS ONE 11(2):e0148628. https://doi.org/10.1371/journal.pone.0148628

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Baek S, Choi CM, Ahn SH, Lee JW, Gong G, Ryu JS, Oh SJ, Bacher-Stier C, Fels L, Koglin N, Hultsch C, Schatz CA, Dinkelborg LM, Mittra ES, Gambhir SS, Moon DH (2012) Exploratory clinical trial of (4S)-4-(3-[18F]fluoropropyl)-l-glutamate for imaging xC- transporter using positron emission tomography in patients with non-small cell lung or breast cancer. Clin Cancer Res 18(19):5427–5437. https://doi.org/10.1158/1078-0432.CCR-12-0214

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Kavanaugh G, Williams J, Morris AS, Nickels ML, Walker R, Koglin N, Stephens AW, Washington MK, Geevarghese SK, Liu Q, Ayers D, Shyr Y, Manning HC (2016) Utility of [(18)F]FSPG PET to image hepatocellular carcinoma: first clinical evaluation in a US population. Mol Imaging Biol 18(6):924–934. https://doi.org/10.1007/s11307-016-1007-0

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Cheng MF, Huang YY, Ho BY, Kuo TC, Hsin LW, Shiue CY, Kuo HC, Jeng YM, Yen RF, Tien YW (2019) Prospective comparison of (4S)-4-(3-(18)F-fluoropropyl)-l-glutamate versus (18)F-fluorodeoxyglucose PET/CT for detecting metastases from pancreatic ductal adenocarcinoma: a proof-of-concept study. Eur J Nucl Med Mol Imaging 46(4):810–820. https://doi.org/10.1007/s00259-018-4251-5

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Joo I, Lee JM, Lee DH, Lee ES, Paeng JC, Lee SJ, Jang JY, Kim SW, Ryu JK, Lee KB (2017) Preoperative assessment of pancreatic cancer with FDG PET/MR imaging versus FDG PET/CT plus contrast-enhanced multidetector CT: a prospective preliminary study. Radiology 282(1):149–159. https://doi.org/10.1148/radiol.2016152798

    Article  PubMed  Google Scholar 

  75. 75.

    Nagamachi S, Nishii R, Wakamatsu H, Mizutani Y, Kiyohara S, Fujita S, Futami S, Sakae T, Furukoji E, Tamura S, Arita H, Chijiiwa K, Kawai K (2013) The usefulness of (18)F-FDG PET/MRI fusion image in diagnosing pancreatic tumor: comparison with (18)F-FDG PET/CT. Ann Nucl Med 27(6):554–563. https://doi.org/10.1007/s12149-013-0719-3

    Article  PubMed  Google Scholar 

  76. 76.

    Tatsumi M, Isohashi K, Onishi H, Hori M, Kim T, Higuchi I, Inoue A, Shimosegawa E, Takeda Y, Hatazawa J (2011) 18F-FDG PET/MRI fusion in characterizing pancreatic tumors: comparison to PET/CT. Int J Clin Oncol 16(4):408–415. https://doi.org/10.1007/s10147-011-0202-x

    Article  PubMed  Google Scholar 

  77. 77.

    Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB (2008) One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 26(18):3063–3072. https://doi.org/10.1200/JCO.2007.15.4377

    Article  PubMed  Google Scholar 

  78. 78.

    Fraenkel M, Kim MK, Faggiano A, Valk GD (2012) Epidemiology of gastroenteropancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol 26(6):691–703. https://doi.org/10.1016/j.bpg.2013.01.006

    CAS  Article  PubMed  Google Scholar 

  79. 79.

    Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, Washington KM, Carneiro F, Cree IA, Board WHOCoTE (2020) The 2019 WHO classification of tumours of the digestive system. Histopathology 76(2):182–188. https://doi.org/10.1111/his.13975

    Article  PubMed  Google Scholar 

  80. 80.

    Dromain C, Deandreis D, Scoazec JY, Goere D, Ducreux M, Baudin E, Tselikas L (2016) Imaging of neuroendocrine tumors of the pancreas. Diagn Interv Imaging 97(12):1241–1257. https://doi.org/10.1016/j.diii.2016.07.012

    CAS  Article  PubMed  Google Scholar 

  81. 81.

    Papotti M, Bongiovanni M, Volante M, Allia 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(5):461–475. https://doi.org/10.1007/s00428-002-0609-x

    CAS  Article  PubMed  Google Scholar 

  82. 82.

    Reubi JC, Waser B (2003) Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging 30(5):781–793. https://doi.org/10.1007/s00259-003-1184-3

    CAS  Article  PubMed  Google Scholar 

  83. 83.

    Poeppel TD, Binse I, Petersenn S, Lahner H, Schott M, Antoch G, Brandau W, Bockisch A, Boy C (2011) 68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. J Nucl Med 52(12):1864–1870. https://doi.org/10.2967/jnumed.111.091165

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Wild D, Bomanji JB, Benkert P, Maecke H, Ell PJ, Reubi JC, Caplin ME (2013) Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT within patients with gastroenteropancreatic neuroendocrine tumors. J Nucl Med 54(3):364–372. https://doi.org/10.2967/jnumed.112.111724

    CAS  Article  PubMed  Google Scholar 

  85. 85.

    Yang J, Kan Y, Ge BH, Yuan L, Li C, Zhao W (2014) Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. Acta Radiol 55(4):389–398. https://doi.org/10.1177/0284185113496679

    Article  PubMed  Google Scholar 

  86. 86.

    Bauckneht M, Albano D, Annunziata S, Santo G, Guglielmo P, Frantellizzi V, Branca A, Ferrari C, Vento A, Mirabile A, Nappi AG, Evangelista L, Alongi P, Laudicella R (2020) Somatostatin receptor PET/CT imaging for the detection and staging of pancreatic NET: a systematic review and meta-analysis. Diagnostics (Basel). https://doi.org/10.3390/diagnostics10080598

    Article  Google Scholar 

  87. 87.

    Bozkurt MF, Virgolini I, Balogova S, Beheshti M, Rubello D, Decristoforo C, Ambrosini V, Kjaer A, Delgado-Bolton R, Kunikowska J, Oyen WJG, Chiti A, Giammarile F, Sundin A, Fanti S (2017) Guideline for PET/CT imaging of neuroendocrine neoplasms with (68)Ga-DOTA-conjugated somatostatin receptor targeting peptides and (18)F-DOPA. Eur J Nucl Med Mol Imaging 44(9):1588–1601. https://doi.org/10.1007/s00259-017-3728-y

    CAS  Article  PubMed  Google Scholar 

  88. 88.

    Pavel M, Oberg K, Falconi M, Krenning EP, Sundin A, Perren A, Berruti A, clinicalguidelines@esmo.org EGCEa (2020) Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 31(7):844–860. https://doi.org/10.1016/j.annonc.2020.03.304

    CAS  Article  PubMed  Google Scholar 

  89. 89.

    Zandee WT, de Herder WW (2018) The evolution of neuroendocrine tumor treatment reflected by ENETS guidelines. Neuroendocrinology 106(4):357–365. https://doi.org/10.1159/000486096

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Chan DL, Pavlakis N, Schembri GP, Bernard EJ, Hsiao E, Hayes A, Barnes T, Diakos C, Khasraw M, Samra J, Eslick E, Roach PJ, Engel A, Clarke SJ, Bailey DL (2017) Dual somatostatin receptor/FDG PET/CT imaging in metastatic neuroendocrine tumours: proposal for a novel grading scheme with prognostic significance. Theranostics 7(5):1149–1158. https://doi.org/10.7150/thno.18068

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Basu S, Ranade R, Thapa P (2015) Correlation and discordance of tumour proliferation index and molecular imaging characteristics and their implications for treatment decisions and outcome pertaining to peptide receptor radionuclide therapy in patients with advanced neuroendocrine tumour: developing a personalized model. Nucl Med Commun 36(8):766–774. https://doi.org/10.1097/MNM.0000000000000321

    CAS  Article  PubMed  Google Scholar 

  92. 92.

    Kumar R, Sharma P, Garg P, Karunanithi S, Naswa N, Sharma R, Thulkar S, Lata S, Malhotra A (2011) Role of (68)Ga-DOTATOC PET-CT in the diagnosis and staging of pancreatic neuroendocrine tumours. Eur Radiol 21(11):2408–2416. https://doi.org/10.1007/s00330-011-2199-y

    Article  PubMed  Google Scholar 

  93. 93.

    Haug AR, Cindea-Drimus R, Auernhammer CJ, Reincke M, Beuschlein F, Wangler B, Uebleis C, Schmidt GP, Spitzweg C, Bartenstein P, Hacker M (2014) Neuroendocrine tumor recurrence: diagnosis with 68Ga-DOTATATE PET/CT. Radiology 270(2):517–525. https://doi.org/10.1148/radiol.13122501

    Article  PubMed  Google Scholar 

  94. 94.

    Johnbeck CB, Knigge U, Loft A, Berthelsen AK, Mortensen J, Oturai P, Langer SW, Elema DR, Kjaer A (2017) Head-to-head comparison of (64)Cu-DOTATATE and (68)Ga-DOTATOC PET/CT: a prospective study of 59 patients with neuroendocrine tumors. J Nucl Med 58(3):451–457. https://doi.org/10.2967/jnumed.116.180430

    CAS  Article  PubMed  Google Scholar 

  95. 95.

    Schraml C, Schwenzer NF, Sperling O, Aschoff P, Lichy MP, Muller M, Brendle C, Werner MK, Claussen CD, Pfannenberg C (2013) Staging of neuroendocrine tumours: comparison of [(6)(8)Ga]DOTATOC multiphase PET/CT and whole-body MRI. Cancer Imaging 13:63–72. https://doi.org/10.1102/1470-7330.2013.0007

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  96. 96.

    Berzaczy D, Giraudo C, Haug AR, Raderer M, Senn D, Karanikas G, Weber M, Mayerhoefer ME (2017) Whole-body 68Ga-DOTANOC PET/MRI Versus 68Ga-DOTANOC PET/CT in patients with neuroendocrine tumors: a prospective study in 28 patients. Clin Nucl Med 42(9):669–674. https://doi.org/10.1097/RLU.0000000000001753

    Article  PubMed  PubMed Central  Google Scholar 

  97. 97.

    Hope TA, Pampaloni MH, Nakakura E, VanBrocklin H, Slater J, Jivan S, Aparici CM, Yee J, Bergsland E (2015) Simultaneous (68)Ga-DOTA-TOC PET/MRI with gadoxetate disodium in patients with neuroendocrine tumor. Abdom Imaging 40(6):1432–1440. https://doi.org/10.1007/s00261-015-0409-9

    Article  PubMed  Google Scholar 

  98. 98.

    Seith F, Schraml C, Reischl G, Nikolaou K, Pfannenberg C, la Fougere C, Schwenzer N (2018) Fast non-enhanced abdominal examination protocols in PET/MRI for patients with neuroendocrine tumors (NET): comparison to multiphase contrast-enhanced PET/CT. Radiol Med 123(11):860–870. https://doi.org/10.1007/s11547-018-0917-0

    Article  PubMed  Google Scholar 

  99. 99.

    Beiderwellen KJ, Poeppel TD, Hartung-Knemeyer V, Buchbender C, Kuehl H, Bockisch A, Lauenstein TC (2013) Simultaneous 68Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic neuroendocrine tumors: initial results. Invest Radiol 48(5):273–279. https://doi.org/10.1097/RLI.0b013e3182871a7f

    CAS  Article  PubMed  Google Scholar 

  100. 100.

    Schmid-Tannwald C, Schmid-Tannwald CM, Morelli JN, Neumann R, Haug AR, Jansen N, Nikolaou K, Schramm N, Reiser MF, Rist C (2013) Comparison of abdominal MRI with diffusion-weighted imaging to 68Ga-DOTATATE PET/CT in detection of neuroendocrine tumors of the pancreas. Eur J Nucl Med Mol Imaging 40(6):897–907. https://doi.org/10.1007/s00259-013-2371-5

    CAS  Article  PubMed  Google Scholar 

  101. 101.

    Etchebehere EC, de Oliveira SA, Gumz B, Vicente A, Hoff PG, Corradi G, Ichiki WA, de Almeida Filho JG, Cantoni S, Camargo EE, Costa FP (2014) 68Ga-DOTATATE PET/CT, 99mTc-HYNIC-octreotide SPECT/CT, and whole-body MR imaging in detection of neuroendocrine tumors: a prospective trial. J Nucl Med 55(10):1598–1604. https://doi.org/10.2967/jnumed.114.144543

    CAS  Article  PubMed  Google Scholar 

  102. 102.

    Naswa N, Sharma P, Gupta SK, Karunanithi S, Reddy RM, Patnecha M, Lata S, Kumar R, Malhotra A, Bal C (2014) Dual tracer functional imaging of gastroenteropancreatic neuroendocrine tumors using 68Ga-DOTA-NOC PET-CT and 18F-FDG PET-CT: competitive or complimentary? Clin Nucl Med 39(1):e27-34. https://doi.org/10.1097/RLU.0b013e31827a216b

    Article  PubMed  Google Scholar 

  103. 103.

    Lewis RB, Lattin GE Jr, Paal E (2010) Pancreatic endocrine tumors: radiologic-clinicopathologic correlation. Radiographics 30(6):1445–1464. https://doi.org/10.1148/rg.306105523

    Article  PubMed  Google Scholar 

  104. 104.

    Binderup T, Knigge U, Loft A, Federspiel B, Kjaer A (2010) 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res 16(3):978–985. https://doi.org/10.1158/1078-0432.CCR-09-1759

    CAS  Article  PubMed  Google Scholar 

  105. 105.

    Panagiotidis E, Alshammari A, Michopoulou S, Skoura E, Naik K, Maragkoudakis E, Mohmaduvesh M, Al-Harbi M, Belda M, Caplin ME, Toumpanakis C, Bomanji J (2017) Comparison of the impact of 68Ga-DOTATATE and 18F-FDG PET/CT on clinical management in patients with neuroendocrine tumors. J Nucl Med 58(1):91–96. https://doi.org/10.2967/jnumed.116.178095

    Article  PubMed  Google Scholar 

  106. 106.

    Garin E, Le Jeune F, Devillers A, Cuggia M, de Lajarte-Thirouard AS, Bouriel C, Boucher E, Raoul JL (2009) Predictive value of 18F-FDG PET and somatostatin receptor scintigraphy in patients with metastatic endocrine tumors. J Nucl Med 50(6):858–864. https://doi.org/10.2967/jnumed.108.057505

    CAS  Article  PubMed  Google Scholar 

  107. 107.

    Fujino M, Aishima S, Shindo K, Oda Y, Morimatsu K, Tsutsumi K, Otsuka T, Tanaka M, Oda Y (2016) Expression of glucose transporter-1 is correlated with hypoxia-inducible factor 1alpha and malignant potential in pancreatic neuroendocrine tumors. Oncol Lett 12(5):3337–3343. https://doi.org/10.3892/ol.2016.5092

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

No funding was received for this review of the literature.

Author information

Affiliations

Authors

Contributions

HD carried out literature search, literature review, content planning, wrote and edited manuscript. RL carried out literature search, literature review, content planning, wrote and edited manuscript. FS carried out literature search, literature review. SB contributed to content planning and editing. LB carried out literature search, literature review, content planning, edited manuscript. AI helped in content planning and edited manuscript.

Corresponding author

Correspondence to R. Laudicella.

Ethics declarations

Conflict of interest

H. Duan, R. Laudicella, F. Stracuzzi, S. Baldari, L. Baratto, and A. Iagaru declare that they have no conflict or competing of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Duan, H., Baratto, L., Laudicella, R. et al. Molecular imaging of pancreatic neoplasms. Clin Transl Imaging (2021). https://doi.org/10.1007/s40336-020-00408-7

Download citation

Keywords

  • Pancreatic cancer
  • Pancreatic neuroendocrine tumor
  • PET/CT
  • PET/MRI
  • FDG
  • Gallium