Real-time fluorescence imaging to identify cholangiocarcinoma in the extrahepatic biliary tree using an enzyme-activatable probe
Introduction Complete resection is the only possible treatment for cholangiocarcinoma in the extrahepatic biliary tree (eCCA), although current imaging modalities are limited in their ability to accurately diagnose longitudinal spread. We aimed to develop fluorescence imaging techniques for real-tim...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2023-04-01
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| Series: | Liver Cancer |
| Online Access: | https://www.karger.com/Article/FullText/530645 |
| _version_ | 1827949304551047168 |
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| author | Ryugen Takahashi Takeaki Ishizawa Yoshinori Inagaki Mariko Tanaka Akira Ogasawara Yugo Kuriki Kyohhei Fujita Mako Kamiya Tetsuo Ushiku Yasuteru Urano Kiyoshi Hasegawa |
| author_facet | Ryugen Takahashi Takeaki Ishizawa Yoshinori Inagaki Mariko Tanaka Akira Ogasawara Yugo Kuriki Kyohhei Fujita Mako Kamiya Tetsuo Ushiku Yasuteru Urano Kiyoshi Hasegawa |
| author_sort | Ryugen Takahashi |
| collection | DOAJ |
| description | Introduction
Complete resection is the only possible treatment for cholangiocarcinoma in the extrahepatic biliary tree (eCCA), although current imaging modalities are limited in their ability to accurately diagnose longitudinal spread. We aimed to develop fluorescence imaging techniques for real-time identification of eCCA using an enzyme-activatable probe, which emits fluorescence immediately after activation by a cancer-specific enzyme.
Methods
Using lysates and small tissue fragments collected from surgically resected specimens, we selected the most specific probe for eCCA from among 800 enzyme-activatable probes. The selected probe was directly sprayed onto resected specimens and fluorescence images were acquired; these images were evaluated for diagnostic accuracy. We also comprehensively searched for enzymes that could activate the probe, then compared their expression levels in cancer and non-cancer tissues.
Results
Analyses of 19 samples (four cancer lysates, seven non-cancer lysates, and eight bile samples) and 54 tissue fragments (13 cancer tissues and 41 non-cancer tissues) revealed that PM-2MeSiR was the most specific fluorophore for eCCA. Fluorescence images of seven patients were obtained; these images enabled rapid identification of cancerous regions, which closely matched histopathology findings in four patients. Puromycin-sensitive aminopeptidase was identified as the enzyme that might activate the probe, and its expression was upregulated in eCCA.
Discussion/Conclusion
Fluorescence imaging with PM-2MeSiR, which may be activated by puromycin-sensitive aminopeptidase, yielded generally high accuracy. This technique may be useful for real-time identification of the spread of eCCA during surgery and endoscopic examinations. |
| first_indexed | 2024-04-09T13:08:22Z |
| format | Article |
| id | doaj.art-bc14c21936f840c6a1b961da8237251f |
| institution | Directory Open Access Journal |
| issn | 2235-1795 1664-5553 |
| language | English |
| last_indexed | 2024-04-09T13:08:22Z |
| publishDate | 2023-04-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Liver Cancer |
| spelling | doaj.art-bc14c21936f840c6a1b961da8237251f2023-05-12T12:24:18ZengKarger PublishersLiver Cancer2235-17951664-55532023-04-0110.1159/000530645530645Real-time fluorescence imaging to identify cholangiocarcinoma in the extrahepatic biliary tree using an enzyme-activatable probeRyugen TakahashiTakeaki IshizawaYoshinori InagakiMariko TanakaAkira OgasawaraYugo KurikiKyohhei FujitaMako KamiyaTetsuo UshikuYasuteru UranoKiyoshi Hasegawahttps://orcid.org/0000-0001-8734-740XIntroduction Complete resection is the only possible treatment for cholangiocarcinoma in the extrahepatic biliary tree (eCCA), although current imaging modalities are limited in their ability to accurately diagnose longitudinal spread. We aimed to develop fluorescence imaging techniques for real-time identification of eCCA using an enzyme-activatable probe, which emits fluorescence immediately after activation by a cancer-specific enzyme. Methods Using lysates and small tissue fragments collected from surgically resected specimens, we selected the most specific probe for eCCA from among 800 enzyme-activatable probes. The selected probe was directly sprayed onto resected specimens and fluorescence images were acquired; these images were evaluated for diagnostic accuracy. We also comprehensively searched for enzymes that could activate the probe, then compared their expression levels in cancer and non-cancer tissues. Results Analyses of 19 samples (four cancer lysates, seven non-cancer lysates, and eight bile samples) and 54 tissue fragments (13 cancer tissues and 41 non-cancer tissues) revealed that PM-2MeSiR was the most specific fluorophore for eCCA. Fluorescence images of seven patients were obtained; these images enabled rapid identification of cancerous regions, which closely matched histopathology findings in four patients. Puromycin-sensitive aminopeptidase was identified as the enzyme that might activate the probe, and its expression was upregulated in eCCA. Discussion/Conclusion Fluorescence imaging with PM-2MeSiR, which may be activated by puromycin-sensitive aminopeptidase, yielded generally high accuracy. This technique may be useful for real-time identification of the spread of eCCA during surgery and endoscopic examinations.https://www.karger.com/Article/FullText/530645 |
| spellingShingle | Ryugen Takahashi Takeaki Ishizawa Yoshinori Inagaki Mariko Tanaka Akira Ogasawara Yugo Kuriki Kyohhei Fujita Mako Kamiya Tetsuo Ushiku Yasuteru Urano Kiyoshi Hasegawa Real-time fluorescence imaging to identify cholangiocarcinoma in the extrahepatic biliary tree using an enzyme-activatable probe Liver Cancer |
| title | Real-time fluorescence imaging to identify cholangiocarcinoma in the extrahepatic biliary tree using an enzyme-activatable probe |
| title_full | Real-time fluorescence imaging to identify cholangiocarcinoma in the extrahepatic biliary tree using an enzyme-activatable probe |
| title_fullStr | Real-time fluorescence imaging to identify cholangiocarcinoma in the extrahepatic biliary tree using an enzyme-activatable probe |
| title_full_unstemmed | Real-time fluorescence imaging to identify cholangiocarcinoma in the extrahepatic biliary tree using an enzyme-activatable probe |
| title_short | Real-time fluorescence imaging to identify cholangiocarcinoma in the extrahepatic biliary tree using an enzyme-activatable probe |
| title_sort | real time fluorescence imaging to identify cholangiocarcinoma in the extrahepatic biliary tree using an enzyme activatable probe |
| url | https://www.karger.com/Article/FullText/530645 |
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