Fluorescent Tissue Site-Selective Lanthanide Chelate, Tb-PCTMB for Enhanced Imaging of Cancer
In-vivo and in-vitro investigations indicate that a newly developed polyazamacrocyclic chelate of Tb(III) has superior properties for use as an abnormal tissue marker. In addition to tissue selectivity, this molecule is unique because of its low toxicity, attractive fluorescent properties, rapid pha...
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Veröffentlicht in: | Analytical chemistry (Washington) 1999-07, Vol.71 (14), p.2607-2615 |
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description | In-vivo and in-vitro investigations indicate that a newly developed polyazamacrocyclic chelate of Tb(III) has superior properties for use as an abnormal tissue marker. In addition to tissue selectivity, this molecule is unique because of its low toxicity, attractive fluorescent properties, rapid pharmokinetics, and relatively high water solubility. The complex Tb-3,6,9-tris(methylene phosphonic acid n-butyl ester)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene (Tb-PCTMB) has also been shown to exhibit strongly shifted emission (Δλ − 280 nm), moving the detection frequency away from autofluorescence backgrounds, and good quantum efficiencies (Φ = 0.51), providing high brightness. Fluorescence imaging was used to quantify Tb-PCTMB at the picomolar level in tissues and to show the significant difference in affinity for the chelate by adenocarcinoma cells HT-29 versus normal epithelial cells (IEC-6). Topical application, or lavage introduction, under endoscopy was used to instill a millimolar aqueous solution of Tb-PCTMB into a dimethylhydrizene-treated Sprague Dawley rat large intestine containing a suspect growth. Subsequent in vitro fluorescence detection and standard histological evaluation confirmed enhanced uptake by adenocarcinoma tissue. Semiquantitative signal interrogation was employed to show the potential for using Tb-PCTMB as a contrast enhancement marker for disease detection. |
doi_str_mv | 10.1021/ac981208u |
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In addition to tissue selectivity, this molecule is unique because of its low toxicity, attractive fluorescent properties, rapid pharmokinetics, and relatively high water solubility. The complex Tb-3,6,9-tris(methylene phosphonic acid n-butyl ester)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene (Tb-PCTMB) has also been shown to exhibit strongly shifted emission (Δλ − 280 nm), moving the detection frequency away from autofluorescence backgrounds, and good quantum efficiencies (Φ = 0.51), providing high brightness. Fluorescence imaging was used to quantify Tb-PCTMB at the picomolar level in tissues and to show the significant difference in affinity for the chelate by adenocarcinoma cells HT-29 versus normal epithelial cells (IEC-6). Topical application, or lavage introduction, under endoscopy was used to instill a millimolar aqueous solution of Tb-PCTMB into a dimethylhydrizene-treated Sprague Dawley rat large intestine containing a suspect growth. Subsequent in vitro fluorescence detection and standard histological evaluation confirmed enhanced uptake by adenocarcinoma tissue. Semiquantitative signal interrogation was employed to show the potential for using Tb-PCTMB as a contrast enhancement marker for disease detection.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/ac981208u</identifier><identifier>PMID: 10424158</identifier><identifier>CODEN: ANCHAM</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Animals ; Biological and medical sciences ; Cancer ; Cell Survival ; Chelating Agents ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Medical imaging ; Medical sciences ; Microscopy, Fluorescence ; Miscellaneous. Technology ; Neoplasms - diagnostic imaging ; Neoplasms - pathology ; Organometallic Compounds ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Radiography ; Rats ; Rats, Sprague-Dawley ; Tumor Cells, Cultured</subject><ispartof>Analytical chemistry (Washington), 1999-07, Vol.71 (14), p.2607-2615</ispartof><rights>Copyright © 1999 American Chemical Society</rights><rights>1999 INIST-CNRS</rights><rights>Copyright American Chemical Society Jul 15, 1999</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a405t-86bafbf74034570af846cfc3055b22899b5da6c93cdcfb3d601e0055d35ed7f63</citedby><cites>FETCH-LOGICAL-a405t-86bafbf74034570af846cfc3055b22899b5da6c93cdcfb3d601e0055d35ed7f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ac981208u$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ac981208u$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1910634$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10424158$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bornhop, Darryl J</creatorcontrib><creatorcontrib>Hubbard, Darren S</creatorcontrib><creatorcontrib>Houlne, Michael P</creatorcontrib><creatorcontrib>Adair, Chris</creatorcontrib><creatorcontrib>Kiefer, Garry E</creatorcontrib><creatorcontrib>Pence, Barbara C</creatorcontrib><creatorcontrib>Morgan, David L</creatorcontrib><title>Fluorescent Tissue Site-Selective Lanthanide Chelate, Tb-PCTMB for Enhanced Imaging of Cancer</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>In-vivo and in-vitro investigations indicate that a newly developed polyazamacrocyclic chelate of Tb(III) has superior properties for use as an abnormal tissue marker. In addition to tissue selectivity, this molecule is unique because of its low toxicity, attractive fluorescent properties, rapid pharmokinetics, and relatively high water solubility. The complex Tb-3,6,9-tris(methylene phosphonic acid n-butyl ester)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene (Tb-PCTMB) has also been shown to exhibit strongly shifted emission (Δλ − 280 nm), moving the detection frequency away from autofluorescence backgrounds, and good quantum efficiencies (Φ = 0.51), providing high brightness. Fluorescence imaging was used to quantify Tb-PCTMB at the picomolar level in tissues and to show the significant difference in affinity for the chelate by adenocarcinoma cells HT-29 versus normal epithelial cells (IEC-6). Topical application, or lavage introduction, under endoscopy was used to instill a millimolar aqueous solution of Tb-PCTMB into a dimethylhydrizene-treated Sprague Dawley rat large intestine containing a suspect growth. Subsequent in vitro fluorescence detection and standard histological evaluation confirmed enhanced uptake by adenocarcinoma tissue. Semiquantitative signal interrogation was employed to show the potential for using Tb-PCTMB as a contrast enhancement marker for disease detection.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Cell Survival</subject><subject>Chelating Agents</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Medical imaging</subject><subject>Medical sciences</subject><subject>Microscopy, Fluorescence</subject><subject>Miscellaneous. Technology</subject><subject>Neoplasms - diagnostic imaging</subject><subject>Neoplasms - pathology</subject><subject>Organometallic Compounds</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Radiography</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Tumor Cells, Cultured</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpl0FFr1TAUB_AgDnedPvgFJIg-CKueJE2aPrqyOwdXHN76KCFNT7bO3nZLWtFvb0Yv22BPgfx_nOT8CXnD4BMDzj5bV2rGQc_PyIpJDpnSmj8nKwAQGS8ADsnLGK8BGAOmXpBDBjnPmdQr8mvdz2PA6HCYaN3FOCPddhNmW-zRTd0fpBs7TFd26Fqk1RX2dsJjWjfZRVV_O6F-DPR0SLHDlp7v7GU3XNLR0-ruJrwiB972EV_vzyPyc31aV1-zzfez8-rLJrM5yCnTqrG-8UUOIpcFWK9z5bwTIGXDuS7LRrZWuVK41vlGtAoYQgpbIbEtvBJH5N0y9yaMtzPGyVyPcxjSk4azQkteakjo44JcGGMM6M1N6HY2_DMMzF2P5r7HZN_uB87NDttHcikugfd7YKOzvQ9p3y4-uJKBEnli2cK6OOHf-9iG30YVopCmvtias7yGH4KfmHXyHxZvXXzY4en__gMESJN_</recordid><startdate>19990715</startdate><enddate>19990715</enddate><creator>Bornhop, Darryl J</creator><creator>Hubbard, Darren S</creator><creator>Houlne, Michael P</creator><creator>Adair, Chris</creator><creator>Kiefer, Garry E</creator><creator>Pence, Barbara C</creator><creator>Morgan, David L</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope></search><sort><creationdate>19990715</creationdate><title>Fluorescent Tissue Site-Selective Lanthanide Chelate, Tb-PCTMB for Enhanced Imaging of Cancer</title><author>Bornhop, Darryl J ; Hubbard, Darren S ; Houlne, Michael P ; Adair, Chris ; Kiefer, Garry E ; Pence, Barbara C ; Morgan, David L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a405t-86bafbf74034570af846cfc3055b22899b5da6c93cdcfb3d601e0055d35ed7f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Cell Survival</topic><topic>Chelating Agents</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Medical imaging</topic><topic>Medical sciences</topic><topic>Microscopy, Fluorescence</topic><topic>Miscellaneous. Technology</topic><topic>Neoplasms - diagnostic imaging</topic><topic>Neoplasms - pathology</topic><topic>Organometallic Compounds</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. 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Chem</addtitle><date>1999-07-15</date><risdate>1999</risdate><volume>71</volume><issue>14</issue><spage>2607</spage><epage>2615</epage><pages>2607-2615</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><coden>ANCHAM</coden><abstract>In-vivo and in-vitro investigations indicate that a newly developed polyazamacrocyclic chelate of Tb(III) has superior properties for use as an abnormal tissue marker. In addition to tissue selectivity, this molecule is unique because of its low toxicity, attractive fluorescent properties, rapid pharmokinetics, and relatively high water solubility. The complex Tb-3,6,9-tris(methylene phosphonic acid n-butyl ester)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene (Tb-PCTMB) has also been shown to exhibit strongly shifted emission (Δλ − 280 nm), moving the detection frequency away from autofluorescence backgrounds, and good quantum efficiencies (Φ = 0.51), providing high brightness. Fluorescence imaging was used to quantify Tb-PCTMB at the picomolar level in tissues and to show the significant difference in affinity for the chelate by adenocarcinoma cells HT-29 versus normal epithelial cells (IEC-6). Topical application, or lavage introduction, under endoscopy was used to instill a millimolar aqueous solution of Tb-PCTMB into a dimethylhydrizene-treated Sprague Dawley rat large intestine containing a suspect growth. Subsequent in vitro fluorescence detection and standard histological evaluation confirmed enhanced uptake by adenocarcinoma tissue. Semiquantitative signal interrogation was employed to show the potential for using Tb-PCTMB as a contrast enhancement marker for disease detection.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>10424158</pmid><doi>10.1021/ac981208u</doi><tpages>9</tpages></addata></record> |
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subjects | Animals Biological and medical sciences Cancer Cell Survival Chelating Agents Humans Investigative techniques, diagnostic techniques (general aspects) Medical imaging Medical sciences Microscopy, Fluorescence Miscellaneous. Technology Neoplasms - diagnostic imaging Neoplasms - pathology Organometallic Compounds Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Radiography Rats Rats, Sprague-Dawley Tumor Cells, Cultured |
title | Fluorescent Tissue Site-Selective Lanthanide Chelate, Tb-PCTMB for Enhanced Imaging of Cancer |
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