Endoscopy 2001; 33(10): 849-853
DOI: 10.1055/s-2001-17328
Original Article

© Georg Thieme Verlag Stuttgart · New York

Detection of Human Gastric Cancer in Resected Specimens Using a Novel Infrared Fluorescent Anti-Human Carcinoembryonic Antigen Antibody with an Infrared Fluorescence Endoscope in Vitro

S. Ito 1 , N. Muguruma 1 , Y. Kusaka 1 , M. Tadatsu 1 , K. Inayama 1 , Y. Musashi 1 , M. Yano 1 , T. Bando 1 , H. Honda 1 , I. Shimizu 1 , K. Ii 1 , K. Takesako 2 , H. Takeuchi 3 , S. Shibamura 3
  • 1 Second Dept. of Internal Medicine, School of Medicine, University of Tokushima, Kuramoto, Tokushima, Japan
  • 2 Dojindo Laboratories, Kumamoto, Japan
  • 3 Daiichi Pure Chemicals Co. Ltd., Tokyo, Japan
Further Information

Publication History

Publication Date:
20 September 2001 (online)

Background and Study Aims: An indocyanine green derivative (ICG-sulfo-OSu) that can be used as an infrared fluorescent labeling substance suitable for detecting microlesions with an infrared fluorescence endoscope has been developed. The aims of the present study were to develop an infrared fluorescence endoscope and to demonstrate its usefulness in detecting cancerous tissue using an antibody coupled with ICG-sulfo-OSu.

Materials and Methods: ICG-sulfo-OSu-labeled mouse anti-human carcinoembryonic antigen (CEA) antibody and an infrared fluorescence endoscope were used in this study. Biopsy specimens of gastric cancer were stained with anti-CEA antibody using the avidin-biotinylated peroxidase complex method. The positive specimens used for the infrared imaging analysis were freshly resected stomachs from three patients.

Results: Treatment of freshly resected stomach specimens with ICG-sulfo-OSu-labeled-anti-CEA antibody complex resulted in positive staining of the tumor sites on infrared fluorescence endoscopy, and the infrared fluorescent images correlated well with the tumor sites.

Conclusions: An anti-CEA antibody with affinity for cancerous lesions and labeled with ICG-sulfo-OSu can therefore be imaged using this infrared fluorescence endoscope. Specific antibodies tagged with ICG-sulfo-OSu can label cancer cells and can generate a strong enough fluorescent signal to detect small cancers when examined with an infrared fluorescence endoscope.

References

  • 1 Tatsuta M, Iishi H, Ichii M, et al. Diagnosis of gastric cancers with fluorescent-labeled monoclonal antibodies to carcinoembryonic antigen.  Lasers Surg Med. 1989;  9 422-426
  • 2 Davies R JH. Ultraviolet radiation damage in DNA.  Biochem Soc Trans. 1995;  23 407-418
  • 3 Williams R J, Narayanan N, Casay G A, et al. Instrument to detect near-infrared fluorescence in solid-phase immunoassay.  Anal Chem. 1994;  66 3102-3107
  • 4 Ito S, Muguruma N, Kakehashi Y, et al. Development of fluorescence-emitting antibody labeling substance by near-infrared ray excitation.  Bioorg Med Chem Lett. 1995;  5 2689-2694
  • 5 Ito S, Muguruma N, Hayashi S, et al. Development of an imaging system using fluorescent labeling substances excited by infrared rays.  Dig Endosc. 1997;  9 278-282
  • 6 Taoka S, Ito S, Muguruma N, et al. Reflected illumination-type imaging system for the development of an infrared fluorescence endoscope.  Dig Endosc. 1999;  11 321-326
  • 7 Muguruma N, Ito S, Hayashi S, et al. Antibodies labeled with fluorescence-agent excitable by infrared rays.  J Gastroenterol. 1998;  33 467-471
  • 8 Ito S, Muguruma N, Hayashi S, et al. Visualization of human gastric cancer with a novel infrared fluorescent labeling marker of anti-CEA antibody.  Dig Endosc. 2000;  12 33-36
  • 9 Hayashi S, Muguruma N, Bando T, et al. Vital immunohistochemical staining for a novel method of diagnosing micro cancer: examination of immunohistochemical staining of nonfixed fresh tissue.  J Med Invest. 1999;  46 178-185
  • 10 Kusaka Y, Ito S, Muguruma N, et al. Vital immunostaining of human gastric and colorectal cancers grafted into nude mice: a preclinical assessment of a potential adjunct to videoendoscopy.  J Gastroenterol. 2000;  35 748-752
  • 11 Byron B, Fisher W G, Waggoner S A, et al. Tumor labeling in vivo using cyanine-conjugated monoclonal antibodies.  Cancer Immunol Immunother. 1995;  41 257-263
  • 12 Byron B, Fisher W G, Hakala R T, et al. Tumor detection and visualization using cyanine fluorochrome-labeled antibodies.  Biotechnol Prog. 1997;  13 649-658
  • 13 Borotto E, Englander J, Pourney C J, et al. Detection of the fluorescence of GI vessels in rats using a CCD camera or a near-infrared video endoscope.  Gastrointest Endosc. 1999;  50 684-688

S. Ito,M.D. 

Second Dept. of Internal Medicine
School of Medicine
University of Tokushima

Kuramoto, Tokushima 770-8503
Japan


Fax: + 81-88-633-9235

Email: ito@clin.med.tokushima-u.ac.jp

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