A Modular Platform for the Rapid Site-Specific Radiolabeling of Proteins with 18F Exemplified by Quantitative Positron Emission Tomography of Human Epidermal Growth Factor Receptor 2
Receptor-specific proteins produced by genetic engineering are attractive as PET imaging agents, but labeling with conventional 18F-based prosthetic groups is problematic due to long synthesis times, poor radiochemical yields, and low specific activities. Therefore, we developed a modular platform f...
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| Veröffentlicht in: | Journal of medicinal chemistry 2009-10, Vol.52 (19), p.5816-5825 |
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| container_issue | 19 |
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| container_title | Journal of medicinal chemistry |
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| creator | Gill, Herman S Tinianow, Jeff N Ogasawara, Annie Flores, Judith E Vanderbilt, Alexander N Raab, Helga Scheer, Justin M Vandlen, Richard Williams, Simon-P Marik, Jan |
| description | Receptor-specific proteins produced by genetic engineering are attractive as PET imaging agents, but labeling with conventional 18F-based prosthetic groups is problematic due to long synthesis times, poor radiochemical yields, and low specific activities. Therefore, we developed a modular platform for the rapid preparation of water-soluble prosthetic groups capable of efficiently introducing 18F into proteins. The utility of this platform is demonstrated by the thiol-specific prosthetic group, [18F]FPEGMA, which was used to produce site-specifically 18F-labeled protein (18F-trastuzumab-ThioFab) in 82 min with a total radiochemical yield of 13 ± 3% and a specific activity of 2.2 ± 0.2 Ci/μmol. 18F-trastuzumab-ThioFab retained the biological activity of native protein and was successfully validated in vivo with microPET imaging of Her2 expression in a xenograft tumor-bearing murine model modulated by the Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin. |
| doi_str_mv | 10.1021/jm900420c |
| format | Article |
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Therefore, we developed a modular platform for the rapid preparation of water-soluble prosthetic groups capable of efficiently introducing 18F into proteins. The utility of this platform is demonstrated by the thiol-specific prosthetic group, [18F]FPEGMA, which was used to produce site-specifically 18F-labeled protein (18F-trastuzumab-ThioFab) in 82 min with a total radiochemical yield of 13 ± 3% and a specific activity of 2.2 ± 0.2 Ci/μmol. 18F-trastuzumab-ThioFab retained the biological activity of native protein and was successfully validated in vivo with microPET imaging of Her2 expression in a xenograft tumor-bearing murine model modulated by the Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm900420c</identifier><identifier>PMID: 19736996</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Columbus, OH: American Chemical Society</publisher><subject>Animals ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Benzoquinones ; Biological and medical sciences ; Contrast media. Radiopharmaceuticals ; Fluorine Radioisotopes ; HSP90 Heat-Shock Proteins - antagonists & inhibitors ; Humans ; Isotope Labeling - methods ; Lactams, Macrocyclic ; Medical sciences ; Mice ; Neoplasms, Experimental - diagnosis ; Pharmacology. Drug treatments ; Positron-Emission Tomography - methods ; Protein Engineering ; Proteins - chemistry ; Receptor, Epidermal Growth Factor - analysis ; Receptor, ErbB-2 - analysis ; Transplantation, Heterologous ; Trastuzumab</subject><ispartof>Journal of medicinal chemistry, 2009-10, Vol.52 (19), p.5816-5825</ispartof><rights>Copyright © 2009 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm900420c$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm900420c$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,27074,27922,27923,56736,56786</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22068419$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19736996$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gill, Herman S</creatorcontrib><creatorcontrib>Tinianow, Jeff N</creatorcontrib><creatorcontrib>Ogasawara, Annie</creatorcontrib><creatorcontrib>Flores, Judith E</creatorcontrib><creatorcontrib>Vanderbilt, Alexander N</creatorcontrib><creatorcontrib>Raab, Helga</creatorcontrib><creatorcontrib>Scheer, Justin M</creatorcontrib><creatorcontrib>Vandlen, Richard</creatorcontrib><creatorcontrib>Williams, Simon-P</creatorcontrib><creatorcontrib>Marik, Jan</creatorcontrib><title>A Modular Platform for the Rapid Site-Specific Radiolabeling of Proteins with 18F Exemplified by Quantitative Positron Emission Tomography of Human Epidermal Growth Factor Receptor 2</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Receptor-specific proteins produced by genetic engineering are attractive as PET imaging agents, but labeling with conventional 18F-based prosthetic groups is problematic due to long synthesis times, poor radiochemical yields, and low specific activities. Therefore, we developed a modular platform for the rapid preparation of water-soluble prosthetic groups capable of efficiently introducing 18F into proteins. The utility of this platform is demonstrated by the thiol-specific prosthetic group, [18F]FPEGMA, which was used to produce site-specifically 18F-labeled protein (18F-trastuzumab-ThioFab) in 82 min with a total radiochemical yield of 13 ± 3% and a specific activity of 2.2 ± 0.2 Ci/μmol. 18F-trastuzumab-ThioFab retained the biological activity of native protein and was successfully validated in vivo with microPET imaging of Her2 expression in a xenograft tumor-bearing murine model modulated by the Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin.</description><subject>Animals</subject><subject>Antibodies, Monoclonal</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Benzoquinones</subject><subject>Biological and medical sciences</subject><subject>Contrast media. Radiopharmaceuticals</subject><subject>Fluorine Radioisotopes</subject><subject>HSP90 Heat-Shock Proteins - antagonists & inhibitors</subject><subject>Humans</subject><subject>Isotope Labeling - methods</subject><subject>Lactams, Macrocyclic</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Neoplasms, Experimental - diagnosis</subject><subject>Pharmacology. Drug treatments</subject><subject>Positron-Emission Tomography - methods</subject><subject>Protein Engineering</subject><subject>Proteins - chemistry</subject><subject>Receptor, Epidermal Growth Factor - analysis</subject><subject>Receptor, ErbB-2 - analysis</subject><subject>Transplantation, Heterologous</subject><subject>Trastuzumab</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkc1uEzEQxy0EoqFw4AWQL3BbGNubzfpYVUmLVERoy3nltceNI-96sb2UvBjPhyNCucyMZn76zxchbxl8ZMDZp_0gAWoO-hlZsCWHqm6hfk4WAJxXvOHijLxKaQ8AgnHxkpwxuRKNlM2C_L6gX4KZvYp061W2IQ60GJp3SG_V5Ay9cxmruwm1s06XnHHBqx69Gx9osHQbQ0Y3Jvro8o6ydkPXv3CYfKHR0P5Av81qzC6r7H4i3YbkcgwjXQ8uJVeC-zCEh6im3eGodj0PqhRLX4yD8vQqhsciu1E6l6FuUeN0DPhr8sIqn_DNyZ-T75v1_eV1dfP16vPlxU2lGKubioEGi0YaIa1E5FyI3mCLta5Nz5agJbMIy9oYe0wYhq3UqxZ0sxLcMhTn5MNf3SmGHzOm3JW5NXqvRgxz6ppVs6rbBgr47gTO_YCmm6IbVDx0_y5dgPcnQCWtvI1q1C49cZxD09ZM_ueUTt0-zHEs-3UMuuOnu6dPiz9-qZsO</recordid><startdate>20091008</startdate><enddate>20091008</enddate><creator>Gill, Herman S</creator><creator>Tinianow, Jeff N</creator><creator>Ogasawara, Annie</creator><creator>Flores, Judith E</creator><creator>Vanderbilt, Alexander N</creator><creator>Raab, Helga</creator><creator>Scheer, Justin M</creator><creator>Vandlen, Richard</creator><creator>Williams, Simon-P</creator><creator>Marik, Jan</creator><general>American Chemical Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20091008</creationdate><title>A Modular Platform for the Rapid Site-Specific Radiolabeling of Proteins with 18F Exemplified by Quantitative Positron Emission Tomography of Human Epidermal Growth Factor Receptor 2</title><author>Gill, Herman S ; Tinianow, Jeff N ; Ogasawara, Annie ; Flores, Judith E ; Vanderbilt, Alexander N ; Raab, Helga ; Scheer, Justin M ; Vandlen, Richard ; Williams, Simon-P ; Marik, Jan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a1146-10c0fed9d39f9ee2233bde8e4c4db150c91fe054ddf4db1d1e89c780c6732f1e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Benzoquinones</topic><topic>Biological and medical sciences</topic><topic>Contrast media. Radiopharmaceuticals</topic><topic>Fluorine Radioisotopes</topic><topic>HSP90 Heat-Shock Proteins - antagonists & inhibitors</topic><topic>Humans</topic><topic>Isotope Labeling - methods</topic><topic>Lactams, Macrocyclic</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Neoplasms, Experimental - diagnosis</topic><topic>Pharmacology. Drug treatments</topic><topic>Positron-Emission Tomography - methods</topic><topic>Protein Engineering</topic><topic>Proteins - chemistry</topic><topic>Receptor, Epidermal Growth Factor - analysis</topic><topic>Receptor, ErbB-2 - analysis</topic><topic>Transplantation, Heterologous</topic><topic>Trastuzumab</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gill, Herman S</creatorcontrib><creatorcontrib>Tinianow, Jeff N</creatorcontrib><creatorcontrib>Ogasawara, Annie</creatorcontrib><creatorcontrib>Flores, Judith E</creatorcontrib><creatorcontrib>Vanderbilt, Alexander N</creatorcontrib><creatorcontrib>Raab, Helga</creatorcontrib><creatorcontrib>Scheer, Justin M</creatorcontrib><creatorcontrib>Vandlen, Richard</creatorcontrib><creatorcontrib>Williams, Simon-P</creatorcontrib><creatorcontrib>Marik, Jan</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gill, Herman S</au><au>Tinianow, Jeff N</au><au>Ogasawara, Annie</au><au>Flores, Judith E</au><au>Vanderbilt, Alexander N</au><au>Raab, Helga</au><au>Scheer, Justin M</au><au>Vandlen, Richard</au><au>Williams, Simon-P</au><au>Marik, Jan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Modular Platform for the Rapid Site-Specific Radiolabeling of Proteins with 18F Exemplified by Quantitative Positron Emission Tomography of Human Epidermal Growth Factor Receptor 2</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2009-10-08</date><risdate>2009</risdate><volume>52</volume><issue>19</issue><spage>5816</spage><epage>5825</epage><pages>5816-5825</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Receptor-specific proteins produced by genetic engineering are attractive as PET imaging agents, but labeling with conventional 18F-based prosthetic groups is problematic due to long synthesis times, poor radiochemical yields, and low specific activities. Therefore, we developed a modular platform for the rapid preparation of water-soluble prosthetic groups capable of efficiently introducing 18F into proteins. The utility of this platform is demonstrated by the thiol-specific prosthetic group, [18F]FPEGMA, which was used to produce site-specifically 18F-labeled protein (18F-trastuzumab-ThioFab) in 82 min with a total radiochemical yield of 13 ± 3% and a specific activity of 2.2 ± 0.2 Ci/μmol. 18F-trastuzumab-ThioFab retained the biological activity of native protein and was successfully validated in vivo with microPET imaging of Her2 expression in a xenograft tumor-bearing murine model modulated by the Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin.</abstract><cop>Columbus, OH</cop><pub>American Chemical Society</pub><pmid>19736996</pmid><doi>10.1021/jm900420c</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Benzoquinones Biological and medical sciences Contrast media. Radiopharmaceuticals Fluorine Radioisotopes HSP90 Heat-Shock Proteins - antagonists & inhibitors Humans Isotope Labeling - methods Lactams, Macrocyclic Medical sciences Mice Neoplasms, Experimental - diagnosis Pharmacology. Drug treatments Positron-Emission Tomography - methods Protein Engineering Proteins - chemistry Receptor, Epidermal Growth Factor - analysis Receptor, ErbB-2 - analysis Transplantation, Heterologous Trastuzumab |
| title | A Modular Platform for the Rapid Site-Specific Radiolabeling of Proteins with 18F Exemplified by Quantitative Positron Emission Tomography of Human Epidermal Growth Factor Receptor 2 |
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