In vivo detection of γ-glutamyl-transferase up-regulation in glioma using hyperpolarized γ-glutamyl-[1-13C]glycine
Glutathione (GSH) is often upregulated in cancer, where it serves to mitigate oxidative stress. γ-glutamyl-transferase (GGT) is a key enzyme in GSH homeostasis, and compared to normal brain its expression is elevated in tumors, including in primary glioblastoma. GGT is therefore an attractive imagin...
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| creator | Batsios, Georgios Najac, Chloé Cao, Peng Viswanath, Pavithra Subramani, Elavarasan Saito, Yutaro Gillespie, Anne Marie Yoshihara, Hikari A. I. Larson, Peder Sando, Shinsuke Ronen, Sabrina M. |
| description | Glutathione (GSH) is often upregulated in cancer, where it serves to mitigate oxidative stress. γ-glutamyl-transferase (GGT) is a key enzyme in GSH homeostasis, and compared to normal brain its expression is elevated in tumors, including in primary glioblastoma. GGT is therefore an attractive imaging target for detection of glioblastoma. The goal of our study was to assess the value of hyperpolarized (HP) γ-glutamyl-[1-
13
C]glycine for non-invasive imaging of glioblastoma. Nude rats bearing orthotopic U87 glioblastoma and healthy controls were investigated. Imaging was performed by injecting HP γ-glutamyl-[1-
13
C]glycine and acquiring dynamic
13
C data on a preclinical 3T MR scanner. The signal-to-noise (SNR) ratios of γ-glutamyl-[1-
13
C]glycine and its product [1-
13
C]glycine were evaluated. Comparison of control and tumor-bearing rats showed no difference in γ-glutamyl-[1-
13
C]glycine SNR, pointing to similar delivery to tumor and normal brain. In contrast, [1-
13
C]glycine SNR was significantly higher in tumor-bearing rats compared to controls, and in tumor regions compared to normal-appearing brain. Importantly, higher [1-
13
C]glycine was associated with higher GGT expression and higher GSH levels in tumor tissue compared to normal brain. Collectively, this study demonstrates, to our knowledge for the first time, the feasibility of using HP γ-glutamyl-[1-
13
C]glycine to monitor GGT expression in the brain and thus to detect glioblastoma. |
| doi_str_mv | 10.1038/s41598-020-63160-y |
| format | Article |
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13
C]glycine for non-invasive imaging of glioblastoma. Nude rats bearing orthotopic U87 glioblastoma and healthy controls were investigated. Imaging was performed by injecting HP γ-glutamyl-[1-
13
C]glycine and acquiring dynamic
13
C data on a preclinical 3T MR scanner. The signal-to-noise (SNR) ratios of γ-glutamyl-[1-
13
C]glycine and its product [1-
13
C]glycine were evaluated. Comparison of control and tumor-bearing rats showed no difference in γ-glutamyl-[1-
13
C]glycine SNR, pointing to similar delivery to tumor and normal brain. In contrast, [1-
13
C]glycine SNR was significantly higher in tumor-bearing rats compared to controls, and in tumor regions compared to normal-appearing brain. Importantly, higher [1-
13
C]glycine was associated with higher GGT expression and higher GSH levels in tumor tissue compared to normal brain. Collectively, this study demonstrates, to our knowledge for the first time, the feasibility of using HP γ-glutamyl-[1-
13
C]glycine to monitor GGT expression in the brain and thus to detect glioblastoma.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-63160-y</identifier><identifier>PMID: 32277103</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1857 ; 631/67/2321 ; 631/67/2327 ; 692/4028/67 ; Amino acids ; Animals ; Brain - diagnostic imaging ; Brain - pathology ; Brain cancer ; Brain tumors ; Carbon Isotopes - administration & dosage ; Carbon Isotopes - chemistry ; Cell Line, Tumor ; Dipeptides - administration & dosage ; Dipeptides - chemistry ; Enzymes ; Feasibility Studies ; gamma-Glutamyltransferase - metabolism ; Gene Expression Regulation, Neoplastic ; Glioblastoma ; Glioblastoma - diagnosis ; Glioblastoma - pathology ; Glioma ; Glutathione ; Glycine ; Homeostasis ; Humanities and Social Sciences ; Humans ; Magnetic Resonance Imaging - methods ; Male ; Metabolism ; Molecular Imaging - methods ; Molecular Probes - administration & dosage ; Molecular Probes - chemistry ; multidisciplinary ; Neuroimaging ; Oxidative stress ; Rats ; Science ; Science (multidisciplinary) ; Tumors ; Up-Regulation ; Xenograft Model Antitumor Assays</subject><ispartof>Scientific reports, 2020-04, Vol.10 (1), p.6244-6244, Article 6244</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-59142e68cf07efa585ff4fa5f9b638cc5913be1d1ef53ea8de5826ffc46b6b233</citedby><cites>FETCH-LOGICAL-c474t-59142e68cf07efa585ff4fa5f9b638cc5913be1d1ef53ea8de5826ffc46b6b233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148357/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148357/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32277103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Batsios, Georgios</creatorcontrib><creatorcontrib>Najac, Chloé</creatorcontrib><creatorcontrib>Cao, Peng</creatorcontrib><creatorcontrib>Viswanath, Pavithra</creatorcontrib><creatorcontrib>Subramani, Elavarasan</creatorcontrib><creatorcontrib>Saito, Yutaro</creatorcontrib><creatorcontrib>Gillespie, Anne Marie</creatorcontrib><creatorcontrib>Yoshihara, Hikari A. I.</creatorcontrib><creatorcontrib>Larson, Peder</creatorcontrib><creatorcontrib>Sando, Shinsuke</creatorcontrib><creatorcontrib>Ronen, Sabrina M.</creatorcontrib><title>In vivo detection of γ-glutamyl-transferase up-regulation in glioma using hyperpolarized γ-glutamyl-[1-13C]glycine</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Glutathione (GSH) is often upregulated in cancer, where it serves to mitigate oxidative stress. γ-glutamyl-transferase (GGT) is a key enzyme in GSH homeostasis, and compared to normal brain its expression is elevated in tumors, including in primary glioblastoma. GGT is therefore an attractive imaging target for detection of glioblastoma. The goal of our study was to assess the value of hyperpolarized (HP) γ-glutamyl-[1-
13
C]glycine for non-invasive imaging of glioblastoma. Nude rats bearing orthotopic U87 glioblastoma and healthy controls were investigated. Imaging was performed by injecting HP γ-glutamyl-[1-
13
C]glycine and acquiring dynamic
13
C data on a preclinical 3T MR scanner. The signal-to-noise (SNR) ratios of γ-glutamyl-[1-
13
C]glycine and its product [1-
13
C]glycine were evaluated. Comparison of control and tumor-bearing rats showed no difference in γ-glutamyl-[1-
13
C]glycine SNR, pointing to similar delivery to tumor and normal brain. In contrast, [1-
13
C]glycine SNR was significantly higher in tumor-bearing rats compared to controls, and in tumor regions compared to normal-appearing brain. Importantly, higher [1-
13
C]glycine was associated with higher GGT expression and higher GSH levels in tumor tissue compared to normal brain. Collectively, this study demonstrates, to our knowledge for the first time, the feasibility of using HP γ-glutamyl-[1-
13
C]glycine to monitor GGT expression in the brain and thus to detect glioblastoma.</description><subject>631/67/1857</subject><subject>631/67/2321</subject><subject>631/67/2327</subject><subject>692/4028/67</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - pathology</subject><subject>Brain cancer</subject><subject>Brain tumors</subject><subject>Carbon Isotopes - administration & dosage</subject><subject>Carbon Isotopes - chemistry</subject><subject>Cell Line, Tumor</subject><subject>Dipeptides - administration & dosage</subject><subject>Dipeptides - chemistry</subject><subject>Enzymes</subject><subject>Feasibility Studies</subject><subject>gamma-Glutamyltransferase - metabolism</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Glioblastoma</subject><subject>Glioblastoma - diagnosis</subject><subject>Glioblastoma - pathology</subject><subject>Glioma</subject><subject>Glutathione</subject><subject>Glycine</subject><subject>Homeostasis</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Male</subject><subject>Metabolism</subject><subject>Molecular Imaging - methods</subject><subject>Molecular Probes - administration & dosage</subject><subject>Molecular Probes - chemistry</subject><subject>multidisciplinary</subject><subject>Neuroimaging</subject><subject>Oxidative stress</subject><subject>Rats</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Tumors</subject><subject>Up-Regulation</subject><subject>Xenograft Model Antitumor Assays</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc1u1TAQhaMK1FalL8ACRWLDxuC_JM4GCV2VUqkSG7qqkOU449SVYwc7uVJ4Ld6DZ6p7byktC7wZy-ebMx6donhN8HuCmfiQOKlagTDFqGakxmg9KI4p5hWijNIXT-5HxWlKtzifiractIfFUX5tmmxzXMwXvtzabSh7mEHPNvgymPL3LzS4ZVbj6tAclU8GokpQLhOKMCxO7UDry8HZMKpySdYP5c06QZyCU9H-hP6ZyTVBhG2-D27V1sOr4qVRLsHpQz0prj6ffdt8QZdfzy82ny6R5g2fUdUSTqEW2uAGjKpEZQzP1bRdzYTWWWcdkJ6AqRgo0UMlaG2M5nVXd5Sxk-Lj3ndauhF6DT4v4-QU7ajiKoOy8rni7Y0cwlY2hAtWNdng3YNBDD8WSLMcbdLgnPIQliQpE0LQtuH3s97-g96GJfq83o5imNY1zhTdUzqGlCKYx88QLO9zlftcZc5V7nKVa25683SNx5Y_KWaA7YGUJT9A_Dv7P7Z3zE6yxg</recordid><startdate>20200410</startdate><enddate>20200410</enddate><creator>Batsios, Georgios</creator><creator>Najac, Chloé</creator><creator>Cao, Peng</creator><creator>Viswanath, Pavithra</creator><creator>Subramani, Elavarasan</creator><creator>Saito, Yutaro</creator><creator>Gillespie, Anne Marie</creator><creator>Yoshihara, Hikari A. 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I.</creatorcontrib><creatorcontrib>Larson, Peder</creatorcontrib><creatorcontrib>Sando, Shinsuke</creatorcontrib><creatorcontrib>Ronen, Sabrina M.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Batsios, Georgios</au><au>Najac, Chloé</au><au>Cao, Peng</au><au>Viswanath, Pavithra</au><au>Subramani, Elavarasan</au><au>Saito, Yutaro</au><au>Gillespie, Anne Marie</au><au>Yoshihara, Hikari A. I.</au><au>Larson, Peder</au><au>Sando, Shinsuke</au><au>Ronen, Sabrina M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo detection of γ-glutamyl-transferase up-regulation in glioma using hyperpolarized γ-glutamyl-[1-13C]glycine</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-04-10</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>6244</spage><epage>6244</epage><pages>6244-6244</pages><artnum>6244</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Glutathione (GSH) is often upregulated in cancer, where it serves to mitigate oxidative stress. γ-glutamyl-transferase (GGT) is a key enzyme in GSH homeostasis, and compared to normal brain its expression is elevated in tumors, including in primary glioblastoma. GGT is therefore an attractive imaging target for detection of glioblastoma. The goal of our study was to assess the value of hyperpolarized (HP) γ-glutamyl-[1-
13
C]glycine for non-invasive imaging of glioblastoma. Nude rats bearing orthotopic U87 glioblastoma and healthy controls were investigated. Imaging was performed by injecting HP γ-glutamyl-[1-
13
C]glycine and acquiring dynamic
13
C data on a preclinical 3T MR scanner. The signal-to-noise (SNR) ratios of γ-glutamyl-[1-
13
C]glycine and its product [1-
13
C]glycine were evaluated. Comparison of control and tumor-bearing rats showed no difference in γ-glutamyl-[1-
13
C]glycine SNR, pointing to similar delivery to tumor and normal brain. In contrast, [1-
13
C]glycine SNR was significantly higher in tumor-bearing rats compared to controls, and in tumor regions compared to normal-appearing brain. Importantly, higher [1-
13
C]glycine was associated with higher GGT expression and higher GSH levels in tumor tissue compared to normal brain. Collectively, this study demonstrates, to our knowledge for the first time, the feasibility of using HP γ-glutamyl-[1-
13
C]glycine to monitor GGT expression in the brain and thus to detect glioblastoma.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32277103</pmid><doi>10.1038/s41598-020-63160-y</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2020-04, Vol.10 (1), p.6244-6244, Article 6244 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 631/67/1857 631/67/2321 631/67/2327 692/4028/67 Amino acids Animals Brain - diagnostic imaging Brain - pathology Brain cancer Brain tumors Carbon Isotopes - administration & dosage Carbon Isotopes - chemistry Cell Line, Tumor Dipeptides - administration & dosage Dipeptides - chemistry Enzymes Feasibility Studies gamma-Glutamyltransferase - metabolism Gene Expression Regulation, Neoplastic Glioblastoma Glioblastoma - diagnosis Glioblastoma - pathology Glioma Glutathione Glycine Homeostasis Humanities and Social Sciences Humans Magnetic Resonance Imaging - methods Male Metabolism Molecular Imaging - methods Molecular Probes - administration & dosage Molecular Probes - chemistry multidisciplinary Neuroimaging Oxidative stress Rats Science Science (multidisciplinary) Tumors Up-Regulation Xenograft Model Antitumor Assays |
| title | In vivo detection of γ-glutamyl-transferase up-regulation in glioma using hyperpolarized γ-glutamyl-[1-13C]glycine |
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