Quantitative receptor-based imaging of tumor proliferation with the sigma-2 ligand [(18)F]ISO-1
The sigma-2 receptor is expressed in higher density in proliferating (P) tumor cells versus quiescent (Q) tumor cells, thus providing an attractive target for imaging the proliferative status (i.e., P:Q ratio) of solid tumors. Here we evaluate the utility of the sigma-2 receptor ligand 2-(2-[(18)F]f...
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| Veröffentlicht in: | PloS one 2013-09, Vol.8 (9), p.e74188 |
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| creator | Shoghi, Kooresh I Xu, Jinbin Su, Yi He, June Rowland, Douglas Yan, Ying Garbow, Joel R Tu, Zhude Jones, Lynne A Higashikubo, Ryuji Wheeler, Kenneth T Lubet, Ronald A Mach, Robert H You, Ming |
| description | The sigma-2 receptor is expressed in higher density in proliferating (P) tumor cells versus quiescent (Q) tumor cells, thus providing an attractive target for imaging the proliferative status (i.e., P:Q ratio) of solid tumors. Here we evaluate the utility of the sigma-2 receptor ligand 2-(2-[(18)F]fluoroethoxy)-N-(4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl)-5-methyl-benzamide, [(18)F]ISO-1, in two different rodent models of breast cancer. In the first study, small animal Positron Emission Tomography (PET) imaging studies were conducted with [(18)F]ISO-1 and (18)FDG in xenografts of mouse mammary tumor 66 and tracer uptake was correlated with the in vivo P:Q ratio determined by flow cytometric measures of BrdU-labeled tumor cells. The second model utilized a chemically-induced (N-methyl-N-nitrosourea [MNU]) model of rat mammary carcinoma to correlate measures of [(18)F]ISO-1 and FDG uptake with MR-based volumetric measures of tumor growth. In addition, [(18)F]ISO-1 and FDG were used to assess the response of MNU-induced tumors to bexarotene and Vorozole therapy. In the mouse mammary 66 tumors, a strong linear correlation was observed between the [(18)F]ISO-1 tumor: background ratio and the proliferative status (P:Q ratio) of the tumor (R = 0.87). Similarly, measures of [(18)F]ISO-1 uptake in MNU-induced tumors significantly correlated (R = 0.68, P |
| doi_str_mv | 10.1371/journal.pone.0074188 |
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Here we evaluate the utility of the sigma-2 receptor ligand 2-(2-[(18)F]fluoroethoxy)-N-(4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl)-5-methyl-benzamide, [(18)F]ISO-1, in two different rodent models of breast cancer. In the first study, small animal Positron Emission Tomography (PET) imaging studies were conducted with [(18)F]ISO-1 and (18)FDG in xenografts of mouse mammary tumor 66 and tracer uptake was correlated with the in vivo P:Q ratio determined by flow cytometric measures of BrdU-labeled tumor cells. The second model utilized a chemically-induced (N-methyl-N-nitrosourea [MNU]) model of rat mammary carcinoma to correlate measures of [(18)F]ISO-1 and FDG uptake with MR-based volumetric measures of tumor growth. In addition, [(18)F]ISO-1 and FDG were used to assess the response of MNU-induced tumors to bexarotene and Vorozole therapy. In the mouse mammary 66 tumors, a strong linear correlation was observed between the [(18)F]ISO-1 tumor: background ratio and the proliferative status (P:Q ratio) of the tumor (R = 0.87). Similarly, measures of [(18)F]ISO-1 uptake in MNU-induced tumors significantly correlated (R = 0.68, P<0.003) with changes in tumor volume between consecutive MR imaging sessions. Our data suggest that PET studies of [(18)F]ISO-1 provide a measure of both the proliferative status and tumor growth rate, which would be valuable in designing an appropriate treatment strategy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0074188</identifier><identifier>PMID: 24073202</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alkylating Agents - toxicity ; Animal models ; Animals ; Anticarcinogenic Agents - therapeutic use ; Apoptosis - drug effects ; Benzamide ; Benzamides ; Bexarotene ; Biology ; Blotting, Western ; Breast cancer ; Cancer ; Cancer therapies ; Carcinoma ; Cell cycle ; Cell growth ; Cell Proliferation - drug effects ; Correlation analysis ; Emission analysis ; Enzymes ; Feasibility studies ; Female ; Flow Cytometry ; Fluorodeoxyglucose F18 ; Glucose ; Growth rate ; Humans ; Image Processing, Computer-Assisted ; In vivo methods and tests ; Kinases ; Ligands ; Magnetic resonance imaging ; Mammary gland ; Mammary Neoplasms, Animal - chemically induced ; Mammary Neoplasms, Animal - diagnostic imaging ; Mammary Neoplasms, Animal - drug therapy ; Mammary Neoplasms, Animal - metabolism ; Medical imaging ; Medicine ; Metabolism ; Methylnitrosourea - toxicity ; Mice ; N-Methyl-N-nitrosourea ; Performance evaluation ; Physicians ; Positron emission ; Positron emission tomography ; Radiopharmaceuticals ; Rats ; Receptors, sigma - metabolism ; Resveratrol ; Retinoids ; Solid tumors ; Surgery ; Target recognition ; Tetrahydronaphthalenes - therapeutic use ; Tomography ; Triazoles - therapeutic use ; Tumor cells ; Tumor Cells, Cultured ; Tumors ; Xenografts</subject><ispartof>PloS one, 2013-09, Vol.8 (9), p.e74188</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c659t-7eeeb5e120d0a36c0c14557c21d2041203cae4a566927acd1b0f694e0168ae003</citedby><cites>FETCH-LOGICAL-c659t-7eeeb5e120d0a36c0c14557c21d2041203cae4a566927acd1b0f694e0168ae003</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/PMC3779213/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779213/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23853,27911,27912,53778,53780,79355,79356</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24073202$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Han, Zhaozhong</contributor><creatorcontrib>Shoghi, Kooresh I</creatorcontrib><creatorcontrib>Xu, Jinbin</creatorcontrib><creatorcontrib>Su, Yi</creatorcontrib><creatorcontrib>He, June</creatorcontrib><creatorcontrib>Rowland, Douglas</creatorcontrib><creatorcontrib>Yan, Ying</creatorcontrib><creatorcontrib>Garbow, Joel R</creatorcontrib><creatorcontrib>Tu, Zhude</creatorcontrib><creatorcontrib>Jones, Lynne A</creatorcontrib><creatorcontrib>Higashikubo, Ryuji</creatorcontrib><creatorcontrib>Wheeler, Kenneth T</creatorcontrib><creatorcontrib>Lubet, Ronald A</creatorcontrib><creatorcontrib>Mach, Robert H</creatorcontrib><creatorcontrib>You, Ming</creatorcontrib><title>Quantitative receptor-based imaging of tumor proliferation with the sigma-2 ligand [(18)F]ISO-1</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The sigma-2 receptor is expressed in higher density in proliferating (P) tumor cells versus quiescent (Q) tumor cells, thus providing an attractive target for imaging the proliferative status (i.e., P:Q ratio) of solid tumors. Here we evaluate the utility of the sigma-2 receptor ligand 2-(2-[(18)F]fluoroethoxy)-N-(4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl)-5-methyl-benzamide, [(18)F]ISO-1, in two different rodent models of breast cancer. In the first study, small animal Positron Emission Tomography (PET) imaging studies were conducted with [(18)F]ISO-1 and (18)FDG in xenografts of mouse mammary tumor 66 and tracer uptake was correlated with the in vivo P:Q ratio determined by flow cytometric measures of BrdU-labeled tumor cells. The second model utilized a chemically-induced (N-methyl-N-nitrosourea [MNU]) model of rat mammary carcinoma to correlate measures of [(18)F]ISO-1 and FDG uptake with MR-based volumetric measures of tumor growth. In addition, [(18)F]ISO-1 and FDG were used to assess the response of MNU-induced tumors to bexarotene and Vorozole therapy. In the mouse mammary 66 tumors, a strong linear correlation was observed between the [(18)F]ISO-1 tumor: background ratio and the proliferative status (P:Q ratio) of the tumor (R = 0.87). Similarly, measures of [(18)F]ISO-1 uptake in MNU-induced tumors significantly correlated (R = 0.68, P<0.003) with changes in tumor volume between consecutive MR imaging sessions. Our data suggest that PET studies of [(18)F]ISO-1 provide a measure of both the proliferative status and tumor growth rate, which would be valuable in designing an appropriate treatment strategy.</description><subject>Alkylating Agents - toxicity</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anticarcinogenic Agents - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>Benzamide</subject><subject>Benzamides</subject><subject>Bexarotene</subject><subject>Biology</subject><subject>Blotting, Western</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Proliferation - drug effects</subject><subject>Correlation analysis</subject><subject>Emission analysis</subject><subject>Enzymes</subject><subject>Feasibility studies</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fluorodeoxyglucose F18</subject><subject>Glucose</subject><subject>Growth rate</subject><subject>Humans</subject><subject>Image Processing, Computer-Assisted</subject><subject>In vivo methods and tests</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Magnetic resonance imaging</subject><subject>Mammary gland</subject><subject>Mammary Neoplasms, Animal - chemically induced</subject><subject>Mammary Neoplasms, Animal - diagnostic imaging</subject><subject>Mammary Neoplasms, Animal - drug therapy</subject><subject>Mammary Neoplasms, Animal - metabolism</subject><subject>Medical imaging</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Methylnitrosourea - toxicity</subject><subject>Mice</subject><subject>N-Methyl-N-nitrosourea</subject><subject>Performance evaluation</subject><subject>Physicians</subject><subject>Positron emission</subject><subject>Positron emission tomography</subject><subject>Radiopharmaceuticals</subject><subject>Rats</subject><subject>Receptors, sigma - metabolism</subject><subject>Resveratrol</subject><subject>Retinoids</subject><subject>Solid tumors</subject><subject>Surgery</subject><subject>Target recognition</subject><subject>Tetrahydronaphthalenes - therapeutic use</subject><subject>Tomography</subject><subject>Triazoles - therapeutic use</subject><subject>Tumor cells</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl-L1DAUxYso7rr6DUQLgrgPHfOvafoiLIurAwuDrvoiEtL0tpOhbWaTdNVvb2anu0xBQfKQcPO7JzeHkyTPMVpgWuC3Gzu6QXWLrR1ggVDBsBAPkmNcUpJxgujDg_NR8sT7DUI5FZw_To4IQwUliBwn8tOohmCCCuYGUgcatsG6rFIe6tT0qjVDm9omDWNvXbp1tjMNuEjbIf1pwjoNa0i9aXuVkbQzrRrq9PsbLE4vfiyvVhl-mjxqVOfh2bSfJF8v3n85_5hdrj4sz88uM83zMmQFAFQ5YIJqpCjXSGOW54UmuCaIxTLVCpjKOS9JoXSNK9TwkgHCXChAiJ4kL_e62856OXnjJWaUMUIFppFY7onaqo3cuvg591taZeRtwbpWKheM7kDqXFGRs0ZUTcMQFaWoBOGkju_yqgQVtd5Nr41VD7WGITjVzUTnN4NZy9beSFoUJbkd5tUk4Oz1CD78Y-SJalWcygyNjWK6N17LM1YILDjGPFKLv1Bx1dAbHdPRmFifNZzOGiIT4Fdo1ei9XF59_n929W3Ovj5g16C6sPa2G3dh8XOQ7UHtrPcOmnvnMJK7cN-5IXfhllO4Y9uLQ9fvm-7STP8AKB7zHg</recordid><startdate>20130920</startdate><enddate>20130920</enddate><creator>Shoghi, Kooresh I</creator><creator>Xu, Jinbin</creator><creator>Su, Yi</creator><creator>He, June</creator><creator>Rowland, Douglas</creator><creator>Yan, Ying</creator><creator>Garbow, Joel R</creator><creator>Tu, Zhude</creator><creator>Jones, Lynne A</creator><creator>Higashikubo, Ryuji</creator><creator>Wheeler, Kenneth T</creator><creator>Lubet, Ronald A</creator><creator>Mach, Robert H</creator><creator>You, Ming</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130920</creationdate><title>Quantitative receptor-based imaging of tumor proliferation with the sigma-2 ligand [(18)F]ISO-1</title><author>Shoghi, Kooresh I ; Xu, Jinbin ; Su, Yi ; He, June ; Rowland, Douglas ; Yan, Ying ; Garbow, Joel R ; Tu, Zhude ; Jones, Lynne A ; Higashikubo, Ryuji ; Wheeler, Kenneth T ; Lubet, Ronald A ; Mach, Robert H ; You, Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c659t-7eeeb5e120d0a36c0c14557c21d2041203cae4a566927acd1b0f694e0168ae003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Alkylating Agents - 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chemically induced</topic><topic>Mammary Neoplasms, Animal - diagnostic imaging</topic><topic>Mammary Neoplasms, Animal - drug therapy</topic><topic>Mammary Neoplasms, Animal - metabolism</topic><topic>Medical imaging</topic><topic>Medicine</topic><topic>Metabolism</topic><topic>Methylnitrosourea - toxicity</topic><topic>Mice</topic><topic>N-Methyl-N-nitrosourea</topic><topic>Performance evaluation</topic><topic>Physicians</topic><topic>Positron emission</topic><topic>Positron emission tomography</topic><topic>Radiopharmaceuticals</topic><topic>Rats</topic><topic>Receptors, sigma - metabolism</topic><topic>Resveratrol</topic><topic>Retinoids</topic><topic>Solid tumors</topic><topic>Surgery</topic><topic>Target recognition</topic><topic>Tetrahydronaphthalenes - therapeutic use</topic><topic>Tomography</topic><topic>Triazoles - therapeutic use</topic><topic>Tumor cells</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shoghi, Kooresh I</creatorcontrib><creatorcontrib>Xu, Jinbin</creatorcontrib><creatorcontrib>Su, Yi</creatorcontrib><creatorcontrib>He, June</creatorcontrib><creatorcontrib>Rowland, Douglas</creatorcontrib><creatorcontrib>Yan, Ying</creatorcontrib><creatorcontrib>Garbow, Joel R</creatorcontrib><creatorcontrib>Tu, Zhude</creatorcontrib><creatorcontrib>Jones, Lynne A</creatorcontrib><creatorcontrib>Higashikubo, Ryuji</creatorcontrib><creatorcontrib>Wheeler, Kenneth T</creatorcontrib><creatorcontrib>Lubet, Ronald A</creatorcontrib><creatorcontrib>Mach, Robert H</creatorcontrib><creatorcontrib>You, Ming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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 China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shoghi, Kooresh I</au><au>Xu, Jinbin</au><au>Su, Yi</au><au>He, June</au><au>Rowland, Douglas</au><au>Yan, Ying</au><au>Garbow, Joel R</au><au>Tu, Zhude</au><au>Jones, Lynne A</au><au>Higashikubo, Ryuji</au><au>Wheeler, Kenneth T</au><au>Lubet, Ronald A</au><au>Mach, Robert H</au><au>You, Ming</au><au>Han, Zhaozhong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantitative receptor-based imaging of tumor proliferation with the sigma-2 ligand [(18)F]ISO-1</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-09-20</date><risdate>2013</risdate><volume>8</volume><issue>9</issue><spage>e74188</spage><pages>e74188-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The sigma-2 receptor is expressed in higher density in proliferating (P) tumor cells versus quiescent (Q) tumor cells, thus providing an attractive target for imaging the proliferative status (i.e., P:Q ratio) of solid tumors. Here we evaluate the utility of the sigma-2 receptor ligand 2-(2-[(18)F]fluoroethoxy)-N-(4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl)-5-methyl-benzamide, [(18)F]ISO-1, in two different rodent models of breast cancer. In the first study, small animal Positron Emission Tomography (PET) imaging studies were conducted with [(18)F]ISO-1 and (18)FDG in xenografts of mouse mammary tumor 66 and tracer uptake was correlated with the in vivo P:Q ratio determined by flow cytometric measures of BrdU-labeled tumor cells. The second model utilized a chemically-induced (N-methyl-N-nitrosourea [MNU]) model of rat mammary carcinoma to correlate measures of [(18)F]ISO-1 and FDG uptake with MR-based volumetric measures of tumor growth. In addition, [(18)F]ISO-1 and FDG were used to assess the response of MNU-induced tumors to bexarotene and Vorozole therapy. In the mouse mammary 66 tumors, a strong linear correlation was observed between the [(18)F]ISO-1 tumor: background ratio and the proliferative status (P:Q ratio) of the tumor (R = 0.87). Similarly, measures of [(18)F]ISO-1 uptake in MNU-induced tumors significantly correlated (R = 0.68, P<0.003) with changes in tumor volume between consecutive MR imaging sessions. Our data suggest that PET studies of [(18)F]ISO-1 provide a measure of both the proliferative status and tumor growth rate, which would be valuable in designing an appropriate treatment strategy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24073202</pmid><doi>10.1371/journal.pone.0074188</doi><tpages>e74188</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-09, Vol.8 (9), p.e74188 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1434423813 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Alkylating Agents - toxicity Animal models Animals Anticarcinogenic Agents - therapeutic use Apoptosis - drug effects Benzamide Benzamides Bexarotene Biology Blotting, Western Breast cancer Cancer Cancer therapies Carcinoma Cell cycle Cell growth Cell Proliferation - drug effects Correlation analysis Emission analysis Enzymes Feasibility studies Female Flow Cytometry Fluorodeoxyglucose F18 Glucose Growth rate Humans Image Processing, Computer-Assisted In vivo methods and tests Kinases Ligands Magnetic resonance imaging Mammary gland Mammary Neoplasms, Animal - chemically induced Mammary Neoplasms, Animal - diagnostic imaging Mammary Neoplasms, Animal - drug therapy Mammary Neoplasms, Animal - metabolism Medical imaging Medicine Metabolism Methylnitrosourea - toxicity Mice N-Methyl-N-nitrosourea Performance evaluation Physicians Positron emission Positron emission tomography Radiopharmaceuticals Rats Receptors, sigma - metabolism Resveratrol Retinoids Solid tumors Surgery Target recognition Tetrahydronaphthalenes - therapeutic use Tomography Triazoles - therapeutic use Tumor cells Tumor Cells, Cultured Tumors Xenografts |
| title | Quantitative receptor-based imaging of tumor proliferation with the sigma-2 ligand [(18)F]ISO-1 |
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