Gd Complexes of Macrocyclic Diethylenetriaminepentaacetic Acid (DTPA) Biphenyl-2,2′-bisamides as Strong Blood-Pool Magnetic Resonance Imaging Contrast Agents
We report the synthesis of macrocyclic DTPA conjugates of 2,2′-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H2O)]·xH2O (2a,b; L = 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2 compares well with those of analogous Gd-DTPA MRI CAs current...
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 2011-08, Vol.54 (15), p.5385-5394 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5394 |
|---|---|
| container_issue | 15 |
| container_start_page | 5385 |
| container_title | Journal of medicinal chemistry |
| container_volume | 54 |
| creator | Jung, Ki-Hye Kim, Hee-Kyung Lee, Gang Ho Kang, Duk-Sik Park, Ji-Ae Kim, Kyeong Min Chang, Yongmin Kim, Tae-Jeong |
| description | We report the synthesis of macrocyclic DTPA conjugates of 2,2′-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H2O)]·xH2O (2a,b; L = 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2 compares well with those of analogous Gd-DTPA MRI CAs currently in use. The present system also shows very high stability in human serum. The R 1 relaxivity reaches 10.9 mM–1 s–1, which is approximately 3 times as high as that of structurally related Gd-DOTA (R 1 = 3.7 mM–1 s–1). The R 1 relaxivity in HSA goes up to 37.2 mM–1 s–1, which is almost twice as high as that of MS-325, a leading BPCA, demonstrating a strong blood pool effect. The in vivo MR images of mice obtained with 2b are coherent, showing strong signal enhancement in heart, abdominal aorta, and small vessels. Even the brain tumor is vividly enhanced for an extended period of time. The structural uniqueness of 2 is that it is neutral in charge and thus makes no resort to electrostatic interaction, supposedly one of the essential factors for the blood-pool effect. |
| doi_str_mv | 10.1021/jm2002052 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_881086836</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>881086836</sourcerecordid><originalsourceid>FETCH-LOGICAL-a314t-e8b381e4b067b1a05ccb4f1241f893c22d4de407083675f724a9d7a80bd619113</originalsourceid><addsrcrecordid>eNptkcFuEzEQQC0EoqFw4AeQLwgqsTD2OrvOMU2hVCqignJeee3Z1JHX3tqORG79k_4Dn8SX4JLSE6eRZt680cwQ8pLBewacfdiMHIDDnD8iMzbnUAkJ4jGZlSSveMPrA_IspQ0A1IzXT8kBZy20IOWM3J4augrj5PAnJhoG-kXpGPROO6vpicV8tXPoMUerRutxQp-V0phLdamtoW9PLi-WR_TYTlfod67i7_jvm19Vb1PhTVGqRL_nGPyaHrsQTHURgitD1v6v4xum4JXXSM9GtbaFWgWfo0qZLtdlVnpOngzKJXxxHw_Jj08fL1efq_Ovp2er5XmlaiZyhbKvJUPRQ9P2TMFc614MjAs2yEWtOTfCoLjbuW7a-dByoRamVRJ607AFY_UhebP3TjFcbzHlbrRJo3PKY9imTkoGsindhTzak-VOKUUcuinaUcVdx6C7e0f38I7Cvrq3bvsRzQP57_4FeL0HlE7dJmyjL0v-R_QHSjaSAQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>881086836</pqid></control><display><type>article</type><title>Gd Complexes of Macrocyclic Diethylenetriaminepentaacetic Acid (DTPA) Biphenyl-2,2′-bisamides as Strong Blood-Pool Magnetic Resonance Imaging Contrast Agents</title><source>MEDLINE</source><source>ACS Publications</source><creator>Jung, Ki-Hye ; Kim, Hee-Kyung ; Lee, Gang Ho ; Kang, Duk-Sik ; Park, Ji-Ae ; Kim, Kyeong Min ; Chang, Yongmin ; Kim, Tae-Jeong</creator><creatorcontrib>Jung, Ki-Hye ; Kim, Hee-Kyung ; Lee, Gang Ho ; Kang, Duk-Sik ; Park, Ji-Ae ; Kim, Kyeong Min ; Chang, Yongmin ; Kim, Tae-Jeong</creatorcontrib><description>We report the synthesis of macrocyclic DTPA conjugates of 2,2′-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H2O)]·xH2O (2a,b; L = 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2 compares well with those of analogous Gd-DTPA MRI CAs currently in use. The present system also shows very high stability in human serum. The R 1 relaxivity reaches 10.9 mM–1 s–1, which is approximately 3 times as high as that of structurally related Gd-DOTA (R 1 = 3.7 mM–1 s–1). The R 1 relaxivity in HSA goes up to 37.2 mM–1 s–1, which is almost twice as high as that of MS-325, a leading BPCA, demonstrating a strong blood pool effect. The in vivo MR images of mice obtained with 2b are coherent, showing strong signal enhancement in heart, abdominal aorta, and small vessels. Even the brain tumor is vividly enhanced for an extended period of time. The structural uniqueness of 2 is that it is neutral in charge and thus makes no resort to electrostatic interaction, supposedly one of the essential factors for the blood-pool effect.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm2002052</identifier><identifier>PMID: 21707088</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Brain Neoplasms - diagnosis ; Cell Line, Tumor ; Contrast Media - chemical synthesis ; Coordination Complexes - chemical synthesis ; Drug Stability ; Gadolinium DTPA - chemistry ; Glioma - diagnosis ; Humans ; Kinetics ; Magnetic Resonance Imaging - methods ; Male ; Mice ; Pentetic Acid - analogs & derivatives ; Pentetic Acid - chemical synthesis ; Pentetic Acid - pharmacology ; Rats ; Serum Albumin - chemistry</subject><ispartof>Journal of medicinal chemistry, 2011-08, Vol.54 (15), p.5385-5394</ispartof><rights>Copyright © 2011 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a314t-e8b381e4b067b1a05ccb4f1241f893c22d4de407083675f724a9d7a80bd619113</citedby><cites>FETCH-LOGICAL-a314t-e8b381e4b067b1a05ccb4f1241f893c22d4de407083675f724a9d7a80bd619113</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/jm2002052$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm2002052$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27078,27926,27927,56740,56790</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21707088$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jung, Ki-Hye</creatorcontrib><creatorcontrib>Kim, Hee-Kyung</creatorcontrib><creatorcontrib>Lee, Gang Ho</creatorcontrib><creatorcontrib>Kang, Duk-Sik</creatorcontrib><creatorcontrib>Park, Ji-Ae</creatorcontrib><creatorcontrib>Kim, Kyeong Min</creatorcontrib><creatorcontrib>Chang, Yongmin</creatorcontrib><creatorcontrib>Kim, Tae-Jeong</creatorcontrib><title>Gd Complexes of Macrocyclic Diethylenetriaminepentaacetic Acid (DTPA) Biphenyl-2,2′-bisamides as Strong Blood-Pool Magnetic Resonance Imaging Contrast Agents</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>We report the synthesis of macrocyclic DTPA conjugates of 2,2′-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H2O)]·xH2O (2a,b; L = 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2 compares well with those of analogous Gd-DTPA MRI CAs currently in use. The present system also shows very high stability in human serum. The R 1 relaxivity reaches 10.9 mM–1 s–1, which is approximately 3 times as high as that of structurally related Gd-DOTA (R 1 = 3.7 mM–1 s–1). The R 1 relaxivity in HSA goes up to 37.2 mM–1 s–1, which is almost twice as high as that of MS-325, a leading BPCA, demonstrating a strong blood pool effect. The in vivo MR images of mice obtained with 2b are coherent, showing strong signal enhancement in heart, abdominal aorta, and small vessels. Even the brain tumor is vividly enhanced for an extended period of time. The structural uniqueness of 2 is that it is neutral in charge and thus makes no resort to electrostatic interaction, supposedly one of the essential factors for the blood-pool effect.</description><subject>Animals</subject><subject>Brain Neoplasms - diagnosis</subject><subject>Cell Line, Tumor</subject><subject>Contrast Media - chemical synthesis</subject><subject>Coordination Complexes - chemical synthesis</subject><subject>Drug Stability</subject><subject>Gadolinium DTPA - chemistry</subject><subject>Glioma - diagnosis</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Male</subject><subject>Mice</subject><subject>Pentetic Acid - analogs & derivatives</subject><subject>Pentetic Acid - chemical synthesis</subject><subject>Pentetic Acid - pharmacology</subject><subject>Rats</subject><subject>Serum Albumin - chemistry</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkcFuEzEQQC0EoqFw4AeQLwgqsTD2OrvOMU2hVCqignJeee3Z1JHX3tqORG79k_4Dn8SX4JLSE6eRZt680cwQ8pLBewacfdiMHIDDnD8iMzbnUAkJ4jGZlSSveMPrA_IspQ0A1IzXT8kBZy20IOWM3J4augrj5PAnJhoG-kXpGPROO6vpicV8tXPoMUerRutxQp-V0phLdamtoW9PLi-WR_TYTlfod67i7_jvm19Vb1PhTVGqRL_nGPyaHrsQTHURgitD1v6v4xum4JXXSM9GtbaFWgWfo0qZLtdlVnpOngzKJXxxHw_Jj08fL1efq_Ovp2er5XmlaiZyhbKvJUPRQ9P2TMFc614MjAs2yEWtOTfCoLjbuW7a-dByoRamVRJ607AFY_UhebP3TjFcbzHlbrRJo3PKY9imTkoGsindhTzak-VOKUUcuinaUcVdx6C7e0f38I7Cvrq3bvsRzQP57_4FeL0HlE7dJmyjL0v-R_QHSjaSAQ</recordid><startdate>20110811</startdate><enddate>20110811</enddate><creator>Jung, Ki-Hye</creator><creator>Kim, Hee-Kyung</creator><creator>Lee, Gang Ho</creator><creator>Kang, Duk-Sik</creator><creator>Park, Ji-Ae</creator><creator>Kim, Kyeong Min</creator><creator>Chang, Yongmin</creator><creator>Kim, Tae-Jeong</creator><general>American Chemical Society</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>7X8</scope></search><sort><creationdate>20110811</creationdate><title>Gd Complexes of Macrocyclic Diethylenetriaminepentaacetic Acid (DTPA) Biphenyl-2,2′-bisamides as Strong Blood-Pool Magnetic Resonance Imaging Contrast Agents</title><author>Jung, Ki-Hye ; Kim, Hee-Kyung ; Lee, Gang Ho ; Kang, Duk-Sik ; Park, Ji-Ae ; Kim, Kyeong Min ; Chang, Yongmin ; Kim, Tae-Jeong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a314t-e8b381e4b067b1a05ccb4f1241f893c22d4de407083675f724a9d7a80bd619113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Brain Neoplasms - diagnosis</topic><topic>Cell Line, Tumor</topic><topic>Contrast Media - chemical synthesis</topic><topic>Coordination Complexes - chemical synthesis</topic><topic>Drug Stability</topic><topic>Gadolinium DTPA - chemistry</topic><topic>Glioma - diagnosis</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Male</topic><topic>Mice</topic><topic>Pentetic Acid - analogs & derivatives</topic><topic>Pentetic Acid - chemical synthesis</topic><topic>Pentetic Acid - pharmacology</topic><topic>Rats</topic><topic>Serum Albumin - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jung, Ki-Hye</creatorcontrib><creatorcontrib>Kim, Hee-Kyung</creatorcontrib><creatorcontrib>Lee, Gang Ho</creatorcontrib><creatorcontrib>Kang, Duk-Sik</creatorcontrib><creatorcontrib>Park, Ji-Ae</creatorcontrib><creatorcontrib>Kim, Kyeong Min</creatorcontrib><creatorcontrib>Chang, Yongmin</creatorcontrib><creatorcontrib>Kim, Tae-Jeong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jung, Ki-Hye</au><au>Kim, Hee-Kyung</au><au>Lee, Gang Ho</au><au>Kang, Duk-Sik</au><au>Park, Ji-Ae</au><au>Kim, Kyeong Min</au><au>Chang, Yongmin</au><au>Kim, Tae-Jeong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gd Complexes of Macrocyclic Diethylenetriaminepentaacetic Acid (DTPA) Biphenyl-2,2′-bisamides as Strong Blood-Pool Magnetic Resonance Imaging Contrast Agents</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2011-08-11</date><risdate>2011</risdate><volume>54</volume><issue>15</issue><spage>5385</spage><epage>5394</epage><pages>5385-5394</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>We report the synthesis of macrocyclic DTPA conjugates of 2,2′-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H2O)]·xH2O (2a,b; L = 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2 compares well with those of analogous Gd-DTPA MRI CAs currently in use. The present system also shows very high stability in human serum. The R 1 relaxivity reaches 10.9 mM–1 s–1, which is approximately 3 times as high as that of structurally related Gd-DOTA (R 1 = 3.7 mM–1 s–1). The R 1 relaxivity in HSA goes up to 37.2 mM–1 s–1, which is almost twice as high as that of MS-325, a leading BPCA, demonstrating a strong blood pool effect. The in vivo MR images of mice obtained with 2b are coherent, showing strong signal enhancement in heart, abdominal aorta, and small vessels. Even the brain tumor is vividly enhanced for an extended period of time. The structural uniqueness of 2 is that it is neutral in charge and thus makes no resort to electrostatic interaction, supposedly one of the essential factors for the blood-pool effect.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>21707088</pmid><doi>10.1021/jm2002052</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2011-08, Vol.54 (15), p.5385-5394 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_881086836 |
| source | MEDLINE; ACS Publications |
| subjects | Animals Brain Neoplasms - diagnosis Cell Line, Tumor Contrast Media - chemical synthesis Coordination Complexes - chemical synthesis Drug Stability Gadolinium DTPA - chemistry Glioma - diagnosis Humans Kinetics Magnetic Resonance Imaging - methods Male Mice Pentetic Acid - analogs & derivatives Pentetic Acid - chemical synthesis Pentetic Acid - pharmacology Rats Serum Albumin - chemistry |
| title | Gd Complexes of Macrocyclic Diethylenetriaminepentaacetic Acid (DTPA) Biphenyl-2,2′-bisamides as Strong Blood-Pool Magnetic Resonance Imaging Contrast Agents |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T09%3A20%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Gd%20Complexes%20of%20Macrocyclic%20Diethylenetriaminepentaacetic%20Acid%20(DTPA)%20Biphenyl-2,2%E2%80%B2-bisamides%20as%20Strong%20Blood-Pool%20Magnetic%20Resonance%20Imaging%20Contrast%20Agents&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Jung,%20Ki-Hye&rft.date=2011-08-11&rft.volume=54&rft.issue=15&rft.spage=5385&rft.epage=5394&rft.pages=5385-5394&rft.issn=0022-2623&rft.eissn=1520-4804&rft_id=info:doi/10.1021/jm2002052&rft_dat=%3Cproquest_cross%3E881086836%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=881086836&rft_id=info:pmid/21707088&rfr_iscdi=true |