Skip to main content
Log in

Feasibility of Using an Enzymatically Activatable Fluorescence Probe for the Rapid Evaluation of Pancreatic Tissue Obtained Using Endoscopic Ultrasound-Guided Fine Needle Aspiration: a Pilot Study

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the most reliable method for the histological diagnosis of pancreatic tumors. Rapid on-site fluorescence-guided histological diagnosis was evaluated by topically applying an enzymatically activatable probe onto the EUS-FNA samples; the probe fluoresces in the presence of γ-glutamyltranspeptidase (GGT).

Procedures

We evaluated GGT expression in pancreatic cancer cell lines in vitro. EUS-FNA was performed in 10 pancreatic tumors. After topical application of the probe, signal intensity was measured using a fluorescence imaging system for 13 min.

Results

GGT was expressed in Panc-1, AsPC-1, and AR42J, but not in KP4 cells. In samples from six cases, several regions of the specimens fluoresced and contained adequate tissue for pathological diagnosis. The remaining four non-fluorescent samples contained very small amounts of carcinoma, normal epithelial cells, or no epithelial cells. The signal intensity at 5 min was 25.5 ± 7.7 and 7.7 ± 0.5 in fluorescent and non-fluorescent regions, respectively (p < 0.05).

Conclusions

Application of enzymatically activatable probe onto EUS-FNA samples would be feasible for the rapid evaluation of tissues suitable for histological diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64:9–29

    Article  PubMed  Google Scholar 

  2. Hewitt MJ, McPhail MJ, Possamai L et al (2012) EUS-guided FNA for diagnosis of solid pancreatic neoplasms: a meta-analysis. Gastrointest Endosc 75:319–331

    Article  PubMed  Google Scholar 

  3. LeBlanc JK, Ciaccia D, Al-Assi MT et al (2004) Optimal number of EUS-guided fine needle passes needed to obtain a correct diagnosis. Gastrointest Endosc 59:475–481

    Article  PubMed  Google Scholar 

  4. Moller K, Papanikolaou IS, Toermer T et al (2009) EUS-guided FNA of solid pancreatic masses: high yield of 2 passes with combined histologic-cytologic analysis. Gastrointest Endosc 70:60–69

    Article  PubMed  Google Scholar 

  5. Iglesias-Garcia J, Dominguez-Munoz JE, Abdulkader I et al (2011) Influence of on-site cytopathology evaluation on the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid pancreatic masses. Am J Gastroenterol 106:1705–1710

    Article  PubMed  Google Scholar 

  6. Schmidt RL, Walker BS, Howard K et al (2013) Rapid on-site evaluation reduces needle passes in endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesions: a risk-benefit analysis. Dig Dis Sci 58:3280–3286

    Article  PubMed  Google Scholar 

  7. Olson MT, Ali SZ (2012) Cytotechnologist on-site evaluation of pancreas fine needle aspiration adequacy: comparison with cytopathologists and correlation with the final interpretation. Acta Cytol 56:340–346

    Article  PubMed  Google Scholar 

  8. Varadarajulu S, Holt BA, Bang JY et al (2015) Training endosonographers in cytopathology: improving the results of EUS-guided FNA. Gastrointest Endosc 81:104–110

    Article  PubMed  Google Scholar 

  9. Urano Y, Asanuma D, Hama Y et al (2009) Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes. Nat Med 15:104–109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kamiya M, Kobayashi H, Hama Y et al (2007) An enzymatically activated fluorescence probe for targeted tumor imaging. J Am Chem Soc 129:3918–3929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Frangioni JV (2008) New technologies for human cancer imaging. J Clin Oncol 26:4012–4021

    Article  PubMed  PubMed Central  Google Scholar 

  12. Urano Y, Sakabe M, Kosaka N et al (2011) Rapid cancer detection by topically spraying a gamma-glutamyltranspeptidase-activated fluorescent probe. Sci Transl Med 3:110ra119

    Article  PubMed  Google Scholar 

  13. Mitsunaga M, Kosaka N, Choyke PL et al (2013) Fluorescence endoscopic detection of murine colitis-associated colon cancer by topically applied enzymatically rapid-activatable probe. Gut 62:1179–1186

    Article  CAS  PubMed  Google Scholar 

  14. Sato C, Abe S, Saito Y et al (2015) A pilot study of fluorescent imaging of colorectal tumors using a gamma-glutamyl-transpeptidase-activatable fluorescent probe. Digestion 91:70–76

    Article  CAS  PubMed  Google Scholar 

  15. Yasuda K, Shiozawa M, Aiso S et al (1990) Distribution of gamma-glutamyl transpeptidase in human pancreas: immunohistochemical study with a monoclonal antibody. J Histochem Cytochem 38:339–350

    Article  CAS  PubMed  Google Scholar 

  16. Beaudoin AR, Grondin G, Laperche Y (1993) Immunocytochemical localization of gamma-glutamyltranspeptidase, GP-2 and amylase in the rat exocrine pancreas: the concept of zymogen granule membrane recycling after exocytosis. J Histochem Cytochem 41:225–233

    Article  CAS  PubMed  Google Scholar 

  17. Battistini B, Chailler P, Briere N, Beaudoin AR (1990) Secretion of gamma-glutamyltranspeptidase by the pancreas: evidence for a membrane shedding process during exocytosis. Life Sci 47:2435–2441

    Article  CAS  PubMed  Google Scholar 

  18. Gerke H, Rizk MK, Vanderheyden AD, Jensen CS (2010) Randomized study comparing endoscopic ultrasound-guided Trucut biopsy and fine needle aspiration with high suction. Cytopathology 21:44–51

    Article  CAS  PubMed  Google Scholar 

  19. Yamashita S, Sakabe M, Ishizawa T et al (2013) Visualization of the leakage of pancreatic juice using a chymotrypsin-activated fluorescent probe. Br J Surg 100:1220–1228

    Article  CAS  PubMed  Google Scholar 

  20. Pompella A, De Tata V, Paolicchi A, Zunino F (2006) Expression of gamma-glutamyltransferase in cancer cells and its significance in drug resistance. Biochem Pharmacol 71:231–238

    Article  CAS  PubMed  Google Scholar 

  21. Urano Y (2013) In vivo cancer detection with a newly designed fluorescent probe. Gan To Kagaku Ryoho 40:299–303

    CAS  PubMed  Google Scholar 

  22. Hanigan MH, Frierson HF Jr, Brown JE et al (1994) Human ovarian tumors express gamma-glutamyl transpeptidase. Cancer Res 54:286–290

    CAS  PubMed  Google Scholar 

  23. Schafer C, Fels C, Brucke M et al (2001) Gamma-glutamyl transferase expression in higher-grade astrocytic glioma. Acta Oncol 40:529–535

    Article  CAS  PubMed  Google Scholar 

  24. Yao D, Jiang D, Huang Z et al (2000) Abnormal expression of hepatoma specific gamma-glutamyl transferase and alteration of gamma-glutamyl transferase gene methylation status in patients with hepatocellular carcinoma. Cancer 88:761–769

    Article  CAS  PubMed  Google Scholar 

  25. Kudo T, Kawakami H, Hayashi T et al (2014) High and low negative pressure suction techniques in EUS-guided fine-needle tissue acquisition by using 25-gauge needles: a multicenter, prospective, randomized, controlled trial. Gastrointest Endosc 80:1030–1037

    Article  PubMed  Google Scholar 

  26. Haba S, Yamao K, Bhatia V et al (2013) Diagnostic ability and factors affecting accuracy of endoscopic ultrasound-guided fine needle aspiration for pancreatic solid lesions: Japanese large single center experience. J Gastroenterol 48:973–981

    Article  PubMed  Google Scholar 

  27. Hayashi T, Ishiwatari H, Yoshida M et al (2013) Rapid on-site evaluation by endosonographer during endoscopic ultrasound-guided fine needle aspiration for pancreatic solid masses. J Gastroenterol Hepatol 28:656–663

    Article  PubMed  Google Scholar 

  28. Harada R, Kato H, Fushimi S et al (2014) An expanded training program for endosonographers improved self-diagnosed accuracy of endoscopic ultrasound-guided fine-needle aspiration cytology of the pancreas. Scand J Gastroenterol 49:1119–1123

    Article  PubMed  Google Scholar 

  29. Iwashita T, Yasuda I, Mukai T et al (2015) Macroscopic on-site quality evaluation of biopsy specimens to improve the diagnostic accuracy during EUS-guided FNA using a 19-gauge needle for solid lesions: a single-center prospective pilot study (MOSE study). Gastrointest Endosc 81:177–185

    Article  PubMed  Google Scholar 

  30. Sakamoto H, Kitano M, Komaki T et al (2009) Prospective comparative study of the EUS guided 25-gauge FNA needle with the 19-gauge Trucut needle and 22-gauge FNA needle in patients with solid pancreatic masses. J Gastroenterol Hepatol 24:384–390

    Article  PubMed  Google Scholar 

  31. Bouvet M, Hoffman RM (2011) Glowing tumors make for better detection and resection. Sci Transl Med 3:110fs10

    Article  PubMed  Google Scholar 

  32. Kishimoto H, Aki R, Urata Y et al (2011) Tumor-selective, adenoviral-mediated GFP genetic labeling of human cancer in the live mouse reports future recurrence after resection. Cell Cycle 10:2737–2741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mekky MA, Yamao K, Sawaki A et al (2010) Diagnostic utility of EUS-guided FNA in patients with gastric submucosal tumors. Gastrointest Endosc 71:913–919

    Article  PubMed  Google Scholar 

  34. Yasuda I, Goto N, Tsurumi H et al (2012) Endoscopic ultrasound-guided fine needle aspiration biopsy for diagnosis of lymphoproliferative disorders: feasibility of immunohistological, flow cytometric, and cytogenetic assessments. Am J Gastroenterol 107:397–404

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Pancreas Research Foundation of Japan (K.K.).

Compliance with Ethical Standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of Interest

The authors declare that they have no conflict of interest.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Shunsuke Ohnishi or Yasuteru Urano.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kawakubo, K., Ohnishi, S., Hatanaka, Y. et al. Feasibility of Using an Enzymatically Activatable Fluorescence Probe for the Rapid Evaluation of Pancreatic Tissue Obtained Using Endoscopic Ultrasound-Guided Fine Needle Aspiration: a Pilot Study. Mol Imaging Biol 18, 463–471 (2016). https://doi.org/10.1007/s11307-015-0898-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-015-0898-5

Key words

Navigation