Evaluation of fluorescence‐guided surgery agents in a murine model of soft tissue fibrosarcoma
Background and Objectives Soft tissue sarcomas (STS) are mesenchymal malignancies. Treatment mainstay is surgical resection with negative margins ± adjuvant treatment. Fluorescence‐guided surgical (FGS) resection can delineate intraoperative margins; FGS has improved oncologic outcomes in other mali...
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| Veröffentlicht in: | Journal of surgical oncology 2018-05, Vol.117 (6), p.1179-1187 |
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| container_title | Journal of surgical oncology |
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| creator | Prince, Andrew C. McGee, Andrew S. Siegel, Herrick Rosenthal, Eben L. Behnke, Nicole K. Warram, Jason M. |
| description | Background and Objectives
Soft tissue sarcomas (STS) are mesenchymal malignancies. Treatment mainstay is surgical resection with negative margins ± adjuvant treatment. Fluorescence‐guided surgical (FGS) resection can delineate intraoperative margins; FGS has improved oncologic outcomes in other malignancies. This novel strategy may minimize resection‐associated morbidity while improving local tumor control.
Methods
We evaluate the tumor‐targeting specificity and utility of fluorescence‐imaging agents to provide disease‐specific contrast. Mice with HT1080 fibrosarcoma tumors received one of five probes: cetuximab‐IRDye800CW (anti‐EGFR), DC101‐IRDye800CW (anti‐VEGFR‐2), IgG‐IRDye800CW, the cathepsin‐activated probe Prosense750EX, or the small molecule probe IntegriSense750. Tumors were imaged daily using open‐ and closed‐field fluorescence imaging systems. Tumor‐to‐background ratios (TBR) were evaluated. On peak TBR days, probe sensitivity was evaluated. Tumors were stained and imaged microscopically.
Results
At peak, closed‐field imaging TBR of cetuximab‐IRDye800CW (16.8) was significantly greater (P |
| doi_str_mv | 10.1002/jso.24950 |
| format | Article |
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Soft tissue sarcomas (STS) are mesenchymal malignancies. Treatment mainstay is surgical resection with negative margins ± adjuvant treatment. Fluorescence‐guided surgical (FGS) resection can delineate intraoperative margins; FGS has improved oncologic outcomes in other malignancies. This novel strategy may minimize resection‐associated morbidity while improving local tumor control.
Methods
We evaluate the tumor‐targeting specificity and utility of fluorescence‐imaging agents to provide disease‐specific contrast. Mice with HT1080 fibrosarcoma tumors received one of five probes: cetuximab‐IRDye800CW (anti‐EGFR), DC101‐IRDye800CW (anti‐VEGFR‐2), IgG‐IRDye800CW, the cathepsin‐activated probe Prosense750EX, or the small molecule probe IntegriSense750. Tumors were imaged daily using open‐ and closed‐field fluorescence imaging systems. Tumor‐to‐background ratios (TBR) were evaluated. On peak TBR days, probe sensitivity was evaluated. Tumors were stained and imaged microscopically.
Results
At peak, closed‐field imaging TBR of cetuximab‐IRDye800CW (16.8) was significantly greater (P < 0.0001) than Integrisense750 (7.0), Prosense750EX (5.8), and DC101‐IRDye800CW (3.7). All agents successfully localized as little as 1.0 mg of tumor tissue in the post‐resection bed; cetuximab‐IRDye800CW generated the greatest contrast (2.5). Cetuximab‐IRDye800CW revealed strong tumor affinity microscopically; tumor fluorescence intensity was significantly greater (P < 0.0004) than 0.2 mm away from tumor border.
Conclusion
This study demonstrates cetuximab‐IRDye800CW superiority. FGS has the potential to improve post‐resection morbidity and mortality by improving disease detection.</description><identifier>ISSN: 0022-4790</identifier><identifier>EISSN: 1096-9098</identifier><identifier>DOI: 10.1002/jso.24950</identifier><identifier>PMID: 29284070</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Cancer surgery ; Fibrosarcoma ; fluorescence ; Monoclonal antibodies ; optical guided surgery ; Sarcoma ; soft tissue sarcoma ; surgical oncology ; Targeted cancer therapy ; Tumors</subject><ispartof>Journal of surgical oncology, 2018-05, Vol.117 (6), p.1179-1187</ispartof><rights>2017 Wiley Periodicals, Inc.</rights><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3530-c9a20361df5aeddfa96cff30049b15e79357ce40ed6305aba30d335010db512f3</citedby><cites>FETCH-LOGICAL-c3530-c9a20361df5aeddfa96cff30049b15e79357ce40ed6305aba30d335010db512f3</cites><orcidid>0000-0002-0390-8116</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjso.24950$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjso.24950$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29284070$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Prince, Andrew C.</creatorcontrib><creatorcontrib>McGee, Andrew S.</creatorcontrib><creatorcontrib>Siegel, Herrick</creatorcontrib><creatorcontrib>Rosenthal, Eben L.</creatorcontrib><creatorcontrib>Behnke, Nicole K.</creatorcontrib><creatorcontrib>Warram, Jason M.</creatorcontrib><title>Evaluation of fluorescence‐guided surgery agents in a murine model of soft tissue fibrosarcoma</title><title>Journal of surgical oncology</title><addtitle>J Surg Oncol</addtitle><description>Background and Objectives
Soft tissue sarcomas (STS) are mesenchymal malignancies. Treatment mainstay is surgical resection with negative margins ± adjuvant treatment. Fluorescence‐guided surgical (FGS) resection can delineate intraoperative margins; FGS has improved oncologic outcomes in other malignancies. This novel strategy may minimize resection‐associated morbidity while improving local tumor control.
Methods
We evaluate the tumor‐targeting specificity and utility of fluorescence‐imaging agents to provide disease‐specific contrast. Mice with HT1080 fibrosarcoma tumors received one of five probes: cetuximab‐IRDye800CW (anti‐EGFR), DC101‐IRDye800CW (anti‐VEGFR‐2), IgG‐IRDye800CW, the cathepsin‐activated probe Prosense750EX, or the small molecule probe IntegriSense750. Tumors were imaged daily using open‐ and closed‐field fluorescence imaging systems. Tumor‐to‐background ratios (TBR) were evaluated. On peak TBR days, probe sensitivity was evaluated. Tumors were stained and imaged microscopically.
Results
At peak, closed‐field imaging TBR of cetuximab‐IRDye800CW (16.8) was significantly greater (P < 0.0001) than Integrisense750 (7.0), Prosense750EX (5.8), and DC101‐IRDye800CW (3.7). All agents successfully localized as little as 1.0 mg of tumor tissue in the post‐resection bed; cetuximab‐IRDye800CW generated the greatest contrast (2.5). Cetuximab‐IRDye800CW revealed strong tumor affinity microscopically; tumor fluorescence intensity was significantly greater (P < 0.0004) than 0.2 mm away from tumor border.
Conclusion
This study demonstrates cetuximab‐IRDye800CW superiority. FGS has the potential to improve post‐resection morbidity and mortality by improving disease detection.</description><subject>Cancer surgery</subject><subject>Fibrosarcoma</subject><subject>fluorescence</subject><subject>Monoclonal antibodies</subject><subject>optical guided surgery</subject><subject>Sarcoma</subject><subject>soft tissue sarcoma</subject><subject>surgical oncology</subject><subject>Targeted cancer therapy</subject><subject>Tumors</subject><issn>0022-4790</issn><issn>1096-9098</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kM1O3TAQRi1UVG5pF7wAstRNuwiM7TiJlwjRPyGxaLt2nXh85askBjsG3V0foc_YJ8H0AgukrmYxZz7Ndwg5YnDCAPjpJoUTXisJe2TFQDWVAtW9Iquy41XdKjggb1LaAIBSTf2aHHDFuxpaWJFfF7dmzGbxYabBUTfmEDENOA_49_efdfYWLU05rjFuqVnjvCTqZ2rolKOfkU7B4vhwmYJb6OJTykid72NIJg5hMm_JvjNjwneP85D8_HTx4_xLdXn1-ev52WU1CCmgGpThIBpmnTRorTOqGZwTALXqmcRWCdkOWAPaRoA0vRFghZDAwPaScScOyYdd7nUMNxnToidfeoyjmTHkpJnqeCe6tmMFff8C3YQc5_Kd5iBb1grV8EJ93FFD6ZIiOn0d_WTiVjPQD9p10a7_aS_s8WNi7ie0z-ST5wKc7oA7P-L2_0n62_erXeQ9UNWNiw</recordid><startdate>20180501</startdate><enddate>20180501</enddate><creator>Prince, Andrew C.</creator><creator>McGee, Andrew S.</creator><creator>Siegel, Herrick</creator><creator>Rosenthal, Eben L.</creator><creator>Behnke, Nicole K.</creator><creator>Warram, Jason M.</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0390-8116</orcidid></search><sort><creationdate>20180501</creationdate><title>Evaluation of fluorescence‐guided surgery agents in a murine model of soft tissue fibrosarcoma</title><author>Prince, Andrew C. ; McGee, Andrew S. ; Siegel, Herrick ; Rosenthal, Eben L. ; Behnke, Nicole K. ; Warram, Jason M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3530-c9a20361df5aeddfa96cff30049b15e79357ce40ed6305aba30d335010db512f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Cancer surgery</topic><topic>Fibrosarcoma</topic><topic>fluorescence</topic><topic>Monoclonal antibodies</topic><topic>optical guided surgery</topic><topic>Sarcoma</topic><topic>soft tissue sarcoma</topic><topic>surgical oncology</topic><topic>Targeted cancer therapy</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Prince, Andrew C.</creatorcontrib><creatorcontrib>McGee, Andrew S.</creatorcontrib><creatorcontrib>Siegel, Herrick</creatorcontrib><creatorcontrib>Rosenthal, Eben L.</creatorcontrib><creatorcontrib>Behnke, Nicole K.</creatorcontrib><creatorcontrib>Warram, Jason M.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Prince, Andrew C.</au><au>McGee, Andrew S.</au><au>Siegel, Herrick</au><au>Rosenthal, Eben L.</au><au>Behnke, Nicole K.</au><au>Warram, Jason M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of fluorescence‐guided surgery agents in a murine model of soft tissue fibrosarcoma</atitle><jtitle>Journal of surgical oncology</jtitle><addtitle>J Surg Oncol</addtitle><date>2018-05-01</date><risdate>2018</risdate><volume>117</volume><issue>6</issue><spage>1179</spage><epage>1187</epage><pages>1179-1187</pages><issn>0022-4790</issn><eissn>1096-9098</eissn><abstract>Background and Objectives
Soft tissue sarcomas (STS) are mesenchymal malignancies. Treatment mainstay is surgical resection with negative margins ± adjuvant treatment. Fluorescence‐guided surgical (FGS) resection can delineate intraoperative margins; FGS has improved oncologic outcomes in other malignancies. This novel strategy may minimize resection‐associated morbidity while improving local tumor control.
Methods
We evaluate the tumor‐targeting specificity and utility of fluorescence‐imaging agents to provide disease‐specific contrast. Mice with HT1080 fibrosarcoma tumors received one of five probes: cetuximab‐IRDye800CW (anti‐EGFR), DC101‐IRDye800CW (anti‐VEGFR‐2), IgG‐IRDye800CW, the cathepsin‐activated probe Prosense750EX, or the small molecule probe IntegriSense750. Tumors were imaged daily using open‐ and closed‐field fluorescence imaging systems. Tumor‐to‐background ratios (TBR) were evaluated. On peak TBR days, probe sensitivity was evaluated. Tumors were stained and imaged microscopically.
Results
At peak, closed‐field imaging TBR of cetuximab‐IRDye800CW (16.8) was significantly greater (P < 0.0001) than Integrisense750 (7.0), Prosense750EX (5.8), and DC101‐IRDye800CW (3.7). All agents successfully localized as little as 1.0 mg of tumor tissue in the post‐resection bed; cetuximab‐IRDye800CW generated the greatest contrast (2.5). Cetuximab‐IRDye800CW revealed strong tumor affinity microscopically; tumor fluorescence intensity was significantly greater (P < 0.0004) than 0.2 mm away from tumor border.
Conclusion
This study demonstrates cetuximab‐IRDye800CW superiority. FGS has the potential to improve post‐resection morbidity and mortality by improving disease detection.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29284070</pmid><doi>10.1002/jso.24950</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-0390-8116</orcidid></addata></record> |
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| subjects | Cancer surgery Fibrosarcoma fluorescence Monoclonal antibodies optical guided surgery Sarcoma soft tissue sarcoma surgical oncology Targeted cancer therapy Tumors |
| title | Evaluation of fluorescence‐guided surgery agents in a murine model of soft tissue fibrosarcoma |
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