Molecular imaging for early prediction of response to Sorafenib treatment in sarcoma
The role of [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET in staging of sarcoma is well established. The aim of this preclinical study was to compare [(18)F]fluorothymidine ([(18)F]FLT) PET to [(18)F]FDG PET regarding early metabolic changes of sarcoma in the course of targeted cancer therapy. SCID mic...
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creator | Li, Zhoulei Herrmann, Ken Pirsig, Sabine Philipp-Abbrederis, Kathrin Henninger, Martin Aichler, Michaela Feuchtinger, Annette Walch, Axel Beer, Ambros J Ringshausen, Ingo Pomykala, Kelsey L Scheidhauer, Klemens Schwaiger, Markus Keller, Ulrich Buck, Andreas K |
description | The role of [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET in staging of sarcoma is well established. The aim of this preclinical study was to compare [(18)F]fluorothymidine ([(18)F]FLT) PET to [(18)F]FDG PET regarding early metabolic changes of sarcoma in the course of targeted cancer therapy. SCID mice bearing sarcoma A673 xenotransplants were used for investigation of tumor response after treatment with the multikinase inhibitor Sorafenib. [(18)F]FLT and/or [(18)F]FDG-PET were performed prior to and early after initiation of treatment. Tumoral uptake (% Injected Dose per gram (%ID/g) of [(18)F]FLT-PET was compared to [(18)F]FDG-PET. Results were correlated with histopathology and in vitro data including cellular uptake, cell cycle-related protein expression, cell cycle distribution and apoptosis. In vitro experiments showed that A673 cells were sensitive to Sorafenib. In vivo, tumor growth was inhibited in comparison to a 4-fold increase of the tumor volume in control mice. Using [(18)F]FDG as tracer, a moderate reduction in tracer uptake (n=15, mean relative %ID/g 74%, range 35%-121%, p=0.03) was observed. The decrease in %ID/g using [(18)F]FLT-PET was significantly higher (p=0.003). The mean relative %ID/g in [(18)F]FLT uptake on day + 5 was significantly reduced to 54% compared to baseline (n=15, range 24%-125%, SD=29%). The PET analysis 24 hr after therapy showed a significant reduction of the mean [(18)F]FLT-%ID/g (p=0.04). The reduction of %ID/g on day + 1 in [(18)F]FDG-PET was not statistically significant (p=0.99). In conclusion, both [(18)F]FDG- and [(18)F]FLT-PET were able to predict response to Sorafenib treatment. In contrast to [(18)F]FDG-PET, [(18)F]FLT-PET was more predictive for very early response to treatment. |
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The aim of this preclinical study was to compare [(18)F]fluorothymidine ([(18)F]FLT) PET to [(18)F]FDG PET regarding early metabolic changes of sarcoma in the course of targeted cancer therapy. SCID mice bearing sarcoma A673 xenotransplants were used for investigation of tumor response after treatment with the multikinase inhibitor Sorafenib. [(18)F]FLT and/or [(18)F]FDG-PET were performed prior to and early after initiation of treatment. Tumoral uptake (% Injected Dose per gram (%ID/g) of [(18)F]FLT-PET was compared to [(18)F]FDG-PET. Results were correlated with histopathology and in vitro data including cellular uptake, cell cycle-related protein expression, cell cycle distribution and apoptosis. In vitro experiments showed that A673 cells were sensitive to Sorafenib. In vivo, tumor growth was inhibited in comparison to a 4-fold increase of the tumor volume in control mice. Using [(18)F]FDG as tracer, a moderate reduction in tracer uptake (n=15, mean relative %ID/g 74%, range 35%-121%, p=0.03) was observed. The decrease in %ID/g using [(18)F]FLT-PET was significantly higher (p=0.003). The mean relative %ID/g in [(18)F]FLT uptake on day + 5 was significantly reduced to 54% compared to baseline (n=15, range 24%-125%, SD=29%). The PET analysis 24 hr after therapy showed a significant reduction of the mean [(18)F]FLT-%ID/g (p=0.04). The reduction of %ID/g on day + 1 in [(18)F]FDG-PET was not statistically significant (p=0.99). In conclusion, both [(18)F]FDG- and [(18)F]FLT-PET were able to predict response to Sorafenib treatment. In contrast to [(18)F]FDG-PET, [(18)F]FLT-PET was more predictive for very early response to treatment.</description><identifier>ISSN: 2160-8407</identifier><identifier>EISSN: 2160-8407</identifier><identifier>PMID: 24380047</identifier><language>eng</language><publisher>United States: e-Century Publishing Corporation</publisher><subject>Original</subject><ispartof>American journal of nuclear medicine and molecular imaging, 2013, Vol.4 (1), p.70-79</ispartof><rights>AJNMMI Copyright © 2014 2014</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867731/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867731/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24380047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Zhoulei</creatorcontrib><creatorcontrib>Herrmann, Ken</creatorcontrib><creatorcontrib>Pirsig, Sabine</creatorcontrib><creatorcontrib>Philipp-Abbrederis, Kathrin</creatorcontrib><creatorcontrib>Henninger, Martin</creatorcontrib><creatorcontrib>Aichler, Michaela</creatorcontrib><creatorcontrib>Feuchtinger, Annette</creatorcontrib><creatorcontrib>Walch, Axel</creatorcontrib><creatorcontrib>Beer, Ambros J</creatorcontrib><creatorcontrib>Ringshausen, Ingo</creatorcontrib><creatorcontrib>Pomykala, Kelsey L</creatorcontrib><creatorcontrib>Scheidhauer, Klemens</creatorcontrib><creatorcontrib>Schwaiger, Markus</creatorcontrib><creatorcontrib>Keller, Ulrich</creatorcontrib><creatorcontrib>Buck, Andreas K</creatorcontrib><title>Molecular imaging for early prediction of response to Sorafenib treatment in sarcoma</title><title>American journal of nuclear medicine and molecular imaging</title><addtitle>Am J Nucl Med Mol Imaging</addtitle><description>The role of [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET in staging of sarcoma is well established. The aim of this preclinical study was to compare [(18)F]fluorothymidine ([(18)F]FLT) PET to [(18)F]FDG PET regarding early metabolic changes of sarcoma in the course of targeted cancer therapy. SCID mice bearing sarcoma A673 xenotransplants were used for investigation of tumor response after treatment with the multikinase inhibitor Sorafenib. [(18)F]FLT and/or [(18)F]FDG-PET were performed prior to and early after initiation of treatment. Tumoral uptake (% Injected Dose per gram (%ID/g) of [(18)F]FLT-PET was compared to [(18)F]FDG-PET. Results were correlated with histopathology and in vitro data including cellular uptake, cell cycle-related protein expression, cell cycle distribution and apoptosis. In vitro experiments showed that A673 cells were sensitive to Sorafenib. In vivo, tumor growth was inhibited in comparison to a 4-fold increase of the tumor volume in control mice. Using [(18)F]FDG as tracer, a moderate reduction in tracer uptake (n=15, mean relative %ID/g 74%, range 35%-121%, p=0.03) was observed. The decrease in %ID/g using [(18)F]FLT-PET was significantly higher (p=0.003). The mean relative %ID/g in [(18)F]FLT uptake on day + 5 was significantly reduced to 54% compared to baseline (n=15, range 24%-125%, SD=29%). The PET analysis 24 hr after therapy showed a significant reduction of the mean [(18)F]FLT-%ID/g (p=0.04). The reduction of %ID/g on day + 1 in [(18)F]FDG-PET was not statistically significant (p=0.99). In conclusion, both [(18)F]FDG- and [(18)F]FLT-PET were able to predict response to Sorafenib treatment. In contrast to [(18)F]FDG-PET, [(18)F]FLT-PET was more predictive for very early response to treatment.</description><subject>Original</subject><issn>2160-8407</issn><issn>2160-8407</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNpVkEtLxDAQgIMo7rLuX5AcvRTyaJvmIsjiC1Y8uJ5LHtMaaZOatML-eyuuss5lBmb4vpk5QUtGS5JVORGnR_UCrVN6J3MUhMhSnqMFy3lFSC6WaPcUOjBTpyJ2vWqdb3ETIgYVuz0eIlhnRhc8Dg2OkIbgE-Ax4JcQVQPeaTxGUGMPfsTO46SiCb26QGeN6hKsD3mFXu9ud5uHbPt8_7i52WYDleWYaaOlYEpYbSUzzErJGRBTUE6kZNwwbgslmLZMzXOGUpKDLvKS50JrW1Z8ha5_uMOke7Bm3iKqrh7ifErc10G5-n_Hu7e6DZ81r0ohOJ0BVwdADB8TpLHuXTLQdcpDmFJNc0kEl4R-uy6PXX-S31fyL5bmczw</recordid><startdate>2013</startdate><enddate>2013</enddate><creator>Li, Zhoulei</creator><creator>Herrmann, Ken</creator><creator>Pirsig, Sabine</creator><creator>Philipp-Abbrederis, Kathrin</creator><creator>Henninger, Martin</creator><creator>Aichler, Michaela</creator><creator>Feuchtinger, Annette</creator><creator>Walch, Axel</creator><creator>Beer, Ambros J</creator><creator>Ringshausen, Ingo</creator><creator>Pomykala, Kelsey L</creator><creator>Scheidhauer, Klemens</creator><creator>Schwaiger, Markus</creator><creator>Keller, Ulrich</creator><creator>Buck, Andreas K</creator><general>e-Century Publishing Corporation</general><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>2013</creationdate><title>Molecular imaging for early prediction of response to Sorafenib treatment in sarcoma</title><author>Li, Zhoulei ; Herrmann, Ken ; Pirsig, Sabine ; Philipp-Abbrederis, Kathrin ; Henninger, Martin ; Aichler, Michaela ; Feuchtinger, Annette ; Walch, Axel ; Beer, Ambros J ; Ringshausen, Ingo ; Pomykala, Kelsey L ; Scheidhauer, Klemens ; Schwaiger, Markus ; Keller, Ulrich ; Buck, Andreas K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p196t-bcb972a7dbd92c2d9932e0c51309923c23d5a72bd2a972c1104eb546347bbd683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Original</topic><toplevel>online_resources</toplevel><creatorcontrib>Li, Zhoulei</creatorcontrib><creatorcontrib>Herrmann, Ken</creatorcontrib><creatorcontrib>Pirsig, Sabine</creatorcontrib><creatorcontrib>Philipp-Abbrederis, Kathrin</creatorcontrib><creatorcontrib>Henninger, Martin</creatorcontrib><creatorcontrib>Aichler, Michaela</creatorcontrib><creatorcontrib>Feuchtinger, Annette</creatorcontrib><creatorcontrib>Walch, Axel</creatorcontrib><creatorcontrib>Beer, Ambros J</creatorcontrib><creatorcontrib>Ringshausen, Ingo</creatorcontrib><creatorcontrib>Pomykala, Kelsey L</creatorcontrib><creatorcontrib>Scheidhauer, Klemens</creatorcontrib><creatorcontrib>Schwaiger, Markus</creatorcontrib><creatorcontrib>Keller, Ulrich</creatorcontrib><creatorcontrib>Buck, Andreas K</creatorcontrib><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of nuclear medicine and molecular imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Zhoulei</au><au>Herrmann, Ken</au><au>Pirsig, Sabine</au><au>Philipp-Abbrederis, Kathrin</au><au>Henninger, Martin</au><au>Aichler, Michaela</au><au>Feuchtinger, Annette</au><au>Walch, Axel</au><au>Beer, Ambros J</au><au>Ringshausen, Ingo</au><au>Pomykala, Kelsey L</au><au>Scheidhauer, Klemens</au><au>Schwaiger, Markus</au><au>Keller, Ulrich</au><au>Buck, Andreas K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular imaging for early prediction of response to Sorafenib treatment in sarcoma</atitle><jtitle>American journal of nuclear medicine and molecular imaging</jtitle><addtitle>Am J Nucl Med Mol Imaging</addtitle><date>2013</date><risdate>2013</risdate><volume>4</volume><issue>1</issue><spage>70</spage><epage>79</epage><pages>70-79</pages><issn>2160-8407</issn><eissn>2160-8407</eissn><abstract>The role of [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET in staging of sarcoma is well established. The aim of this preclinical study was to compare [(18)F]fluorothymidine ([(18)F]FLT) PET to [(18)F]FDG PET regarding early metabolic changes of sarcoma in the course of targeted cancer therapy. SCID mice bearing sarcoma A673 xenotransplants were used for investigation of tumor response after treatment with the multikinase inhibitor Sorafenib. [(18)F]FLT and/or [(18)F]FDG-PET were performed prior to and early after initiation of treatment. Tumoral uptake (% Injected Dose per gram (%ID/g) of [(18)F]FLT-PET was compared to [(18)F]FDG-PET. Results were correlated with histopathology and in vitro data including cellular uptake, cell cycle-related protein expression, cell cycle distribution and apoptosis. In vitro experiments showed that A673 cells were sensitive to Sorafenib. In vivo, tumor growth was inhibited in comparison to a 4-fold increase of the tumor volume in control mice. Using [(18)F]FDG as tracer, a moderate reduction in tracer uptake (n=15, mean relative %ID/g 74%, range 35%-121%, p=0.03) was observed. The decrease in %ID/g using [(18)F]FLT-PET was significantly higher (p=0.003). The mean relative %ID/g in [(18)F]FLT uptake on day + 5 was significantly reduced to 54% compared to baseline (n=15, range 24%-125%, SD=29%). The PET analysis 24 hr after therapy showed a significant reduction of the mean [(18)F]FLT-%ID/g (p=0.04). The reduction of %ID/g on day + 1 in [(18)F]FDG-PET was not statistically significant (p=0.99). In conclusion, both [(18)F]FDG- and [(18)F]FLT-PET were able to predict response to Sorafenib treatment. In contrast to [(18)F]FDG-PET, [(18)F]FLT-PET was more predictive for very early response to treatment.</abstract><cop>United States</cop><pub>e-Century Publishing Corporation</pub><pmid>24380047</pmid><tpages>10</tpages></addata></record> |
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title | Molecular imaging for early prediction of response to Sorafenib treatment in sarcoma |
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