Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study

Authors: Takeshi Mizushima, Shunsuke Ohnishi, Yuichi Shimizu, Yutaka Hatanaka, Kanako C. Hatanaka, Hidetaka Hosono, Yoshimasa Kubota, Mitsuteru Natsuizaka, Mako Kamiya, Shouko Ono, Akihiro Homma, Mototsugu Kato, Naoya Sakamoto, Yasuteru Urano

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

Detecting superficial head and neck squamous cell carcinoma (HNSCC) by endoscopy is challenging because of limited morphological hallmarks, and iodine cannot be applied to head and neck lesions due to severe mucosal irritation. γ-glutamyltranspeptidase (GGT), a cell surface enzyme, is overexpressed in several cancers, and it has been reported that γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent targeting agent which can be enzymatically activated and becomes fluorescent after cleavage of a GGT-specific sequence, can be activated within a few minutes after application to animal models. We investigated whether early HNSCC can be detected by applying gGlu-HMRG to clinical samples.

Methods

gGlu-HMRG was applied to four HNSCC cell lines, and fluorescence was observed by fluorescence microscopy and flow cytometry. Immunohistological examination was performed in three recent cases of endoscopic submucosal dissection (ESD) to investigate GGT expression. Fluorescence imaging with gGlu-HMRG in eight clinical samples resected by ESD or surgery was performed, and fluorescence intensity of tumor and normal mucosa regions of interest (ROI) was prospectively measured.

Results

All four gGlu-HMRG-applied cell lines emitted green fluorescence. Immunohistological examination demonstrated that GGT was highly expressed in HNSCC of the recent three ESD cases but barely in the normal mucosa. Fluorescence imaging showed that iodine-voiding lesions became fluorescent within a few minutes after application of gGlu-HMRG in all eight resected tumors. Tumor ROI fluorescence intensity was significantly higher than in the normal mucosa five minutes after gGlu-HMRG application.

Conclusions

Fluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC.
Literature
1.
Vigneswaran N, Williams MD. Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am. 2014;26(2):123–41.CrossRefPubMedPubMedCentral
2.
Johansen LV, Grau C, Overgaard J. Hypopharyngeal squamous cell carcinoma--treatment results in 138 consecutively admitted patients. Acta Oncol. 2000;39(4):529–36.CrossRefPubMed
3.
Eckel HE, Staar S, Volling P, Sittel C, Damm M, Jungehuelsing M. Surgical treatment for hypopharynx carcinoma: feasibility, mortality, and results. Otolaryngol Head Neck Surg. 2001;124(5):561–9.CrossRefPubMed
4.
Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. The Lancet. 2008;371(9625):1695–709.CrossRef
5.
Muto M, Nakane M, Katada C, Sano Y, Ohtsu A, Esumi H, et al. Squamous cell carcinoma in situ at oropharyngeal and hypopharyngeal mucosal sites. Cancer. 2004;101(6):1375–81.CrossRefPubMed
6.
Carvalho R, Areia M, Brito D, Saraiva S, Alves S, Cadime AT. Diagnostic accuracy of lugol chromoendoscopy in the oesophagus in patients with head and neck cancer. Rev Esp Enferm Dig. 2013;105(2):79–83.CrossRefPubMed
7.
Fagundes RB, de Barros SG, Putten AC, Mello ES, Wagner M, Bassi LA, et al. Occult dysplasia is disclosed by Lugol chromoendoscopy in alcoholics at high risk for squamous cell carcinoma of the esophagus. Endoscopy. 1999;31(4):281–5.CrossRefPubMed
8.
Hori K, Okada H, Kawahara Y, Takenaka R, Shimizu S, Ohno Y, et al. Lugol-voiding lesions are an important risk factor for a second primary squamous cell carcinoma in patients with esosphageal cancer or head and neck cancer. Am J Gastroenterol. 2011;106(5):858–66.CrossRefPubMed
9.
Hanaoka N, Ishihara R, Takeuchi Y, Suzuki M, Uemura H, Fujii T, et al. Clinical outcomes of endoscopic mucosal resection and endoscopic submucosal dissection as a transoral treatment for superficial pharyngeal cancer. Head Neck. 2013;35(9):1248–54.CrossRefPubMed
10.
Muto M, Minashi K, Yano T, Saito Y, Oda I, Nonaka S, et al. Early detection of superficial squamous cell carcinoma in the head and neck region and esophagus by narrow band imaging: a multicenter randomized controlled trial. J Clin Oncol. 2010;28(9):1566–72.CrossRefPubMedPubMedCentral
11.
Suzuki H, Saito Y, Ikehara H, Oda I. Evaluation of visualization of squamous cell carcinoma of esophagus and pharynx using an autofluorescence imaging videoendoscope system. J Gastroenterol Hepatol. 2009;24(12):1834–9.CrossRefPubMed
12.
Pompella A, De Tata V, Paolicchi A, Zunino F. Expression of gamma-glutamyltransferase in cancer cells and its significance in drug resistance. Biochem Pharmacol. 2006;71(3):231–8.CrossRefPubMed
13.
Schafer C, Fels C, Brucke M, Holzhausen HJ, Bahn H, Wellman M, et al. Gamma-glutamyl transferase expression in higher-grade astrocytic glioma. Acta Oncol. 2001;40(4):529–35.CrossRefPubMed
14.
Yao D, Jiang D, Huang Z, Lu J, Tao Q, Yu Z, et al. Abnormal expression of hepatoma specific gamma-glutamyl transferase and alteration of gamma-glutamyl transferase gene methylation status in patients with hepatocellular carcinoma. Cancer. 2000;88(4):761–9.CrossRefPubMed
15.
Hanigan MH, Frierson Jr HF, Brown JE, Lovell MA, Taylor PT. Human ovarian tumors express gamma-glutamyl transpeptidase. Cancer Res. 1994;54(1):286–90.PubMed
16.
Urano Y, Sakabe M, Kosaka N, Ogawa M, Mitsunaga M, Asanuma D, et al. Rapid cancer detection by topically spraying a gamma-glutamyltranspeptidase-activated fluorescent probe. Sci Transl Med. 2011;3(110):110ra19.CrossRef
17.
Mitsunaga M, Kosaka N, Choyke PL, Young MR, Dextras CR, Saud SM, et al. Fluorescence endoscopic detection of murine colitis-associated colon cancer by topically applied enzymatically rapid-activatable probe. Gut. 2013;62(8):1179–86.CrossRefPubMed
18.
Kamiya M, Asanuma D, Kuranaga E, Takeishi A, Sakabe M, Miura M, et al. beta-Galactosidase fluorescence probe with improved cellular accumulation based on a spirocyclized rhodol scaffold. J Am Chem Soc. 2011;133(33):12960–3.CrossRefPubMed
19.
Shimizu Y, Yamamoto J, Kato M, Yoshida T, Hirota J, Ono Y, et al. Endoscopic submucosal dissection for treatment of early stage hypopharyngeal carcinoma. Gastrointest Endosc. 2006;64(2):255–9. discussion 60–2.CrossRefPubMed
20.
21.
Watanabe A, Taniguchi M, Tsujie H, Hosokawa M, Fujita M, Sasaki S. The value of narrow band imaging for early detection of laryngeal cancer. Eur Arch Otorhinolaryngol. 2009;266(7):1017–23.CrossRefPubMed
22.
Goda K, Dobashi A, Tajiri H. Perspectives on narrow-band imaging endoscopy for superficial squamous neoplasms of the orohypopharynx and esophagus. Dig Endosc. 2014;26 Suppl 1:1–11.CrossRefPubMed
23.
Dobre M, Poenaru M, Balica NC, Doros CI. Detection of early laryngeal cancer and its precursor lesions by a real-time autofluorescence imaging system. Rom J Morphol Embryol. 2014;55(4):1377–81.PubMed
24.
Nonaka S, Saito Y, Oda I, Kozu T, Saito D. Narrow-band imaging endoscopy with magnification is useful for detecting metachronous superficial pharyngeal cancer in patients with esophageal squamous cell carcinoma. J Gastroenterol Hepatol. 2010;25(2):264–9.CrossRefPubMed
25.
Katada C, Tanabe S, Koizumi W, Higuchi K, Sasaki T, Azuma M, et al. Narrow band imaging for detecting superficial squamous cell carcinoma of the head and neck in patients with esophageal squamous cell carcinoma. Endoscopy. 2010;42(3):185–90.CrossRefPubMed
26.
Arens C, Reussner D, Woenkhaus J, Leunig A, Betz CS, Glanz H. Indirect fluorescence laryngoscopy in the diagnosis of precancerous and cancerous laryngeal lesions. Eur Arch Otorhinolaryngol. 2007;264(6):621–6.CrossRefPubMed
27.
Ishihara R, Takeuchi Y, Chatani R, Kidu T, Inoue T, Hanaoka N, et al. Prospective evaluation of narrow-band imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia in experienced and less experienced endoscopists. Dis Esophagus. 2010;23(6):480–6.CrossRefPubMed
28.
Sato C, Abe S, Saito Y, So Tsuruki E, Takamaru H, Makazu M, et al. A pilot study of fluorescent imaging of colorectal tumors using a gamma-glutamyl-transpeptidase-activatable fluorescent probe. Digestion. 2015;91(1):70–6.CrossRefPubMed
Metadata
Title
Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study
Authors
Takeshi Mizushima
Shunsuke Ohnishi
Yuichi Shimizu
Yutaka Hatanaka
Kanako C. Hatanaka
Hidetaka Hosono
Yoshimasa Kubota
Mitsuteru Natsuizaka
Mako Kamiya
Shouko Ono
Akihiro Homma
Mototsugu Kato
Naoya Sakamoto
Yasuteru Urano
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2421-z

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue

Research article

Induction Chemotherapy Followed by Radiotherapy versus Concurrent Chemoradiotherapy in elderly patients with nasopharyngeal carcinoma: finding from a propensity-matched analysis

Research article

Melanoma-specific mortality and competing mortality in patients with non-metastatic malignant melanoma: a population-based analysis

Research article

Distribution and prognosis of uncommon metastases from non-small cell lung cancer

Case report

A case report of a patient with metastatic ocular melanoma who experienced a response to treatment with the BRAF inhibitor vemurafenib

Research article

The role of GAGE cancer/testis antigen in metastasis: the jury is still out

Research article

Bile acids destabilise HIF-1α and promote anti-tumour phenotypes in cancer cell models
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits