DOTAGA-trastuzumab. A new antibody conjugate targeting HER2/Neu antigen for diagnostic purposes.
Identifieur interne : 000F21 ( Main/Exploration ); précédent : 000F20; suivant : 000F22DOTAGA-trastuzumab. A new antibody conjugate targeting HER2/Neu antigen for diagnostic purposes.
Auteurs : RBID : pubmed:22519915Abstract
Improved bifunctional chelating agents (BFC) are required for indium-111 radiolabeling of monoclonal antibodies (mAbs) under mild conditions to yield stable, target-specific agents. 2,2',2"-(10-(2,6-Dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (DOTAGA-anhydride) was evaluated for mAb conjugation and labeling with indium-111. The DOTA analogue was synthesized and conjugated to trastuzumab-which targets the HER2/neu receptor-in mild conditions (PBS pH 7.4, 25 °C, 30 min) and gave a mean degree of conjugation of 2.6 macrocycle per antibody. Labeling of this immunoconjugate with indium-111 was performed in 75% yield after 1 h at 37 °C, and the proportion of (111)In-DOTAGA-trastuzumab reached 97% after purification. The affinity of DOTAGA-trastuzumab was 5.5 ± 0.6 nM as evaluated by in vitro saturation assays using HCC1954 breast cancer cell line. SPECT/CT imaging and biodistribution studies were performed in mice bearing breast cancer BT-474 xenografts. BT-474 tumors were clearly visualized on SPECT images at 24, 48, and 72 h postinjection. The tumor uptake of [(111)In-DOTAGA]-trastuzumab reached 65%ID/g 72 h postinjection. These results show that the DOTAGA BFC appears to be a valuable tool for biologics conjugation.
DOI: 10.1021/bc200680x
PubMed: 22519915
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A new antibody conjugate targeting HER2/Neu antigen for diagnostic purposes.</title><author><name sortKey="Moreau, Mathieu" uniqKey="Moreau M">Mathieu Moreau</name><affiliation wicri:level="3"><nlm:affiliation>Institut de Chimie Moléculaire de l'Université de Bourgogne , UMR CNRS 6302, 21078 Dijon Cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Chimie Moléculaire de l'Université de Bourgogne , UMR CNRS 6302, 21078 Dijon Cedex</wicri:regionArea><placeName><region type="region" nuts="2">Bourgogne</region><settlement type="city">Dijon</settlement></placeName></affiliation></author><author><name sortKey="Raguin, Olivier" uniqKey="Raguin O">Olivier Raguin</name></author><author><name sortKey="Vrigneaud, Jean Marc" uniqKey="Vrigneaud J">Jean-Marc Vrigneaud</name></author><author><name sortKey="Collin, Bertrand" uniqKey="Collin B">Bertrand Collin</name></author><author><name sortKey="Bernhard, Claire" uniqKey="Bernhard C">Claire Bernhard</name></author><author><name sortKey="Tizon, Xavier" uniqKey="Tizon X">Xavier Tizon</name></author><author><name sortKey="Boschetti, Frederic" uniqKey="Boschetti F">Frédéric Boschetti</name></author><author><name sortKey="Duchamp, Olivier" uniqKey="Duchamp O">Olivier Duchamp</name></author><author><name sortKey="Brunotte, Francois" uniqKey="Brunotte F">François Brunotte</name></author><author><name sortKey="Denat, Franck" uniqKey="Denat F">Franck Denat</name></author></titleStmt><publicationStmt><date when="2012">2012</date><idno type="doi">10.1021/bc200680x</idno><idno type="RBID">pubmed:22519915</idno><idno type="pmid">22519915</idno><idno type="wicri:Area/Main/Corpus">000D63</idno><idno type="wicri:Area/Main/Curation">000D63</idno><idno type="wicri:Area/Main/Exploration">000F21</idno></publicationStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Improved bifunctional chelating agents (BFC) are required for indium-111 radiolabeling of monoclonal antibodies (mAbs) under mild conditions to yield stable, target-specific agents. 2,2',2"-(10-(2,6-Dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (DOTAGA-anhydride) was evaluated for mAb conjugation and labeling with indium-111. The DOTA analogue was synthesized and conjugated to trastuzumab-which targets the HER2/neu receptor-in mild conditions (PBS pH 7.4, 25 °C, 30 min) and gave a mean degree of conjugation of 2.6 macrocycle per antibody. Labeling of this immunoconjugate with indium-111 was performed in 75% yield after 1 h at 37 °C, and the proportion of (111)In-DOTAGA-trastuzumab reached 97% after purification. The affinity of DOTAGA-trastuzumab was 5.5 ± 0.6 nM as evaluated by in vitro saturation assays using HCC1954 breast cancer cell line. SPECT/CT imaging and biodistribution studies were performed in mice bearing breast cancer BT-474 xenografts. BT-474 tumors were clearly visualized on SPECT images at 24, 48, and 72 h postinjection. The tumor uptake of [(111)In-DOTAGA]-trastuzumab reached 65%ID/g 72 h postinjection. These results show that the DOTAGA BFC appears to be a valuable tool for biologics conjugation.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="In-Process"><PMID Version="1">22519915</PMID><DateCreated><Year>2014</Year><Month>02</Month><Day>04</Day></DateCreated><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1520-4812</ISSN><JournalIssue CitedMedium="Internet"><Volume>23</Volume><Issue>6</Issue><PubDate><Year>2012</Year><Month>Jun</Month><Day>20</Day></PubDate></JournalIssue><Title>Bioconjugate chemistry</Title><ISOAbbreviation>Bioconjug. Chem.</ISOAbbreviation></Journal><ArticleTitle>DOTAGA-trastuzumab. A new antibody conjugate targeting HER2/Neu antigen for diagnostic purposes.</ArticleTitle><Pagination><MedlinePgn>1181-8</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/bc200680x</ELocationID><Abstract><AbstractText>Improved bifunctional chelating agents (BFC) are required for indium-111 radiolabeling of monoclonal antibodies (mAbs) under mild conditions to yield stable, target-specific agents. 2,2',2"-(10-(2,6-Dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (DOTAGA-anhydride) was evaluated for mAb conjugation and labeling with indium-111. The DOTA analogue was synthesized and conjugated to trastuzumab-which targets the HER2/neu receptor-in mild conditions (PBS pH 7.4, 25 °C, 30 min) and gave a mean degree of conjugation of 2.6 macrocycle per antibody. Labeling of this immunoconjugate with indium-111 was performed in 75% yield after 1 h at 37 °C, and the proportion of (111)In-DOTAGA-trastuzumab reached 97% after purification. The affinity of DOTAGA-trastuzumab was 5.5 ± 0.6 nM as evaluated by in vitro saturation assays using HCC1954 breast cancer cell line. SPECT/CT imaging and biodistribution studies were performed in mice bearing breast cancer BT-474 xenografts. BT-474 tumors were clearly visualized on SPECT images at 24, 48, and 72 h postinjection. The tumor uptake of [(111)In-DOTAGA]-trastuzumab reached 65%ID/g 72 h postinjection. These results show that the DOTAGA BFC appears to be a valuable tool for biologics conjugation.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Moreau</LastName><ForeName>Mathieu</ForeName><Initials>M</Initials><Affiliation>Institut de Chimie Moléculaire de l'Université de Bourgogne , UMR CNRS 6302, 21078 Dijon Cedex, France.</Affiliation></Author><Author ValidYN="Y"><LastName>Raguin</LastName><ForeName>Olivier</ForeName><Initials>O</Initials></Author><Author ValidYN="Y"><LastName>Vrigneaud</LastName><ForeName>Jean-Marc</ForeName><Initials>JM</Initials></Author><Author ValidYN="Y"><LastName>Collin</LastName><ForeName>Bertrand</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Bernhard</LastName><ForeName>Claire</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Tizon</LastName><ForeName>Xavier</ForeName><Initials>X</Initials></Author><Author ValidYN="Y"><LastName>Boschetti</LastName><ForeName>Frédéric</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Duchamp</LastName><ForeName>Olivier</ForeName><Initials>O</Initials></Author><Author ValidYN="Y"><LastName>Brunotte</LastName><ForeName>François</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Denat</LastName><ForeName>Franck</ForeName><Initials>F</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType><PublicationType>Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2012</Year><Month>05</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Bioconjug Chem</MedlineTA><NlmUniqueID>9010319</NlmUniqueID><ISSNLinking>1043-1802</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="aheadofprint"><Year>2012</Year><Month>5</Month><Day>9</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>4</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>4</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>4</Month><Day>24</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1021/bc200680x</ArticleId><ArticleId IdType="pubmed">22519915</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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