Trastuzumab labeled to high specific activity with ¹¹¹In by conjugation to G4 PAMAM dendrimers derivatized with multiple DTPA chelators exhibits increased cytotoxic potency on HER2-positive breast cancer cells.
Identifieur interne : 000306 ( Main/Exploration ); précédent : 000305; suivant : 000307Trastuzumab labeled to high specific activity with ¹¹¹In by conjugation to G4 PAMAM dendrimers derivatized with multiple DTPA chelators exhibits increased cytotoxic potency on HER2-positive breast cancer cells.
Auteurs : RBID : pubmed:23615858English descriptors
- KwdEn :
- Antibodies, Monoclonal, Humanized (chemistry), Antibodies, Monoclonal, Humanized (pharmacology), Antineoplastic Agents (chemistry), Antineoplastic Agents (pharmacology), Breast Neoplasms (drug therapy), Breast Neoplasms (immunology), Cell Line, Tumor, Cell Survival (drug effects), Chelating Agents (chemistry), Dendrimers (chemistry), Female, Humans, Indium Radioisotopes (chemistry), Nylons (chemistry), Pentetic Acid (chemistry), Receptor, erbB-2 (immunology).
- MESH :
- chemical , chemistry : Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Chelating Agents, Dendrimers, Indium Radioisotopes, Nylons, Pentetic Acid.
- chemical , immunology : Receptor, erbB-2.
- chemical , pharmacology : Antibodies, Monoclonal, Humanized, Antineoplastic Agents.
- drug effects : Cell Survival.
- drug therapy : Breast Neoplasms.
- immunology : Breast Neoplasms.
- Cell Line, Tumor, Female, Humans.
Abstract
To conjugate trastuzumab with/without NLS peptides to G4 PAMAM dendrimers derivatized with DTPA and determine the specific radioactivity (SA) for (111)In labeling, HER2 immunoreactivity and cytotoxicity on breast cancer (BC) cells.
DOI: 10.1007/s11095-013-1044-1
PubMed: 23615858
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Trastuzumab labeled to high specific activity with ¹¹¹In by conjugation to G4 PAMAM dendrimers derivatized with multiple DTPA chelators exhibits increased cytotoxic potency on HER2-positive breast cancer cells.</title><author><name sortKey="Chan, Conrad" uniqKey="Chan C">Conrad Chan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmaceutical Sciences, University of Toronto, 144 College St., Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Pharmaceutical Sciences, University of Toronto, 144 College St., Toronto, Ontario</wicri:regionArea></affiliation></author><author><name sortKey="Cai, Zhongli" uniqKey="Cai Z">Zhongli Cai</name></author><author><name sortKey="Reilly, Raymond M" uniqKey="Reilly R">Raymond M Reilly</name></author></titleStmt><publicationStmt><date when="2013">2013</date><idno type="doi">10.1007/s11095-013-1044-1</idno><idno type="RBID">pubmed:23615858</idno><idno type="pmid">23615858</idno><idno type="wicri:Area/Main/Corpus">000659</idno><idno type="wicri:Area/Main/Curation">000659</idno><idno type="wicri:Area/Main/Exploration">000306</idno></publicationStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Monoclonal, Humanized (chemistry)</term><term>Antibodies, Monoclonal, Humanized (pharmacology)</term><term>Antineoplastic Agents (chemistry)</term><term>Antineoplastic Agents (pharmacology)</term><term>Breast Neoplasms (drug therapy)</term><term>Breast Neoplasms (immunology)</term><term>Cell Line, Tumor</term><term>Cell Survival (drug effects)</term><term>Chelating Agents (chemistry)</term><term>Dendrimers (chemistry)</term><term>Female</term><term>Humans</term><term>Indium Radioisotopes (chemistry)</term><term>Nylons (chemistry)</term><term>Pentetic Acid (chemistry)</term><term>Receptor, erbB-2 (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Antineoplastic Agents</term><term>Chelating Agents</term><term>Dendrimers</term><term>Indium Radioisotopes</term><term>Nylons</term><term>Pentetic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Receptor, erbB-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Antineoplastic Agents</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Breast Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Female</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">To conjugate trastuzumab with/without NLS peptides to G4 PAMAM dendrimers derivatized with DTPA and determine the specific radioactivity (SA) for (111)In labeling, HER2 immunoreactivity and cytotoxicity on breast cancer (BC) cells.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">23615858</PMID><DateCreated><Year>2013</Year><Month>07</Month><Day>01</Day></DateCreated><DateCompleted><Year>2014</Year><Month>01</Month><Day>27</Day></DateCompleted><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1573-904X</ISSN><JournalIssue CitedMedium="Internet"><Volume>30</Volume><Issue>8</Issue><PubDate><Year>2013</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Pharmaceutical research</Title><ISOAbbreviation>Pharm. Res.</ISOAbbreviation></Journal><ArticleTitle>Trastuzumab labeled to high specific activity with ¹¹¹In by conjugation to G4 PAMAM dendrimers derivatized with multiple DTPA chelators exhibits increased cytotoxic potency on HER2-positive breast cancer cells.</ArticleTitle><Pagination><MedlinePgn>1999-2009</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s11095-013-1044-1</ELocationID><Abstract><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">To conjugate trastuzumab with/without NLS peptides to G4 PAMAM dendrimers derivatized with DTPA and determine the specific radioactivity (SA) for (111)In labeling, HER2 immunoreactivity and cytotoxicity on breast cancer (BC) cells.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">G4 dendrimers were reacted with DTPA then conjugated through a thiol to maleimide-derivatized trastuzumab. The SA achievable was determined by incubating 2 to 20 μg with 60 MBq of (111)In. HER2 immunoreactivity, internalization and nuclear importation were measured. The effect of (111)In-DTPA-G4-trastuzumab (5.9 MBq/μg) on the clonogenic survival (CS) of SK-Br-3 or MDA-MB-231 cells with high or low HER2 density, respectively was compared to (111)In-DTPA-NLS-trastuzumab (0.5 MBq/μg). DNA double-strand breaks (DSBs) were measured.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">DTPA-G4-trastuzumab was labeled with (111)In to a SA (23.6 MBq/μg) which was 100-fold higher than (111)In-DTPA-NLS-trastuzumab. (111)In-DTPA-G4-trastuzumab and (111)In-DTPA-G4-NLS-trastuzumab retained HER2 immunoreactivity and were internalized and imported into the nucleus of BC cells. G4-radioimmunoconjugates were 2-4 fold and 9-fold more cytotoxic to SK-Br-3 and MDA-MB-231 cells, respectively than (111)In-DTPA-NLS-trastuzumab which was associated with an increase in DNA DSBs.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Conjugation of trastuzumab to G4 PAMAM dendrimers modified with 30 DTPA permitted high SA (111)In labeling which increased their cytotoxic potency for BC cells with high or low HER2 density.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Conrad</ForeName><Initials>C</Initials><Affiliation>Department of Pharmaceutical Sciences, University of Toronto, 144 College St., Toronto, Ontario, Canada.</Affiliation></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Zhongli</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Reilly</LastName><ForeName>Raymond M</ForeName><Initials>RM</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>2013</Year><Month>04</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Pharm Res</MedlineTA><NlmUniqueID>8406521</NlmUniqueID><ISSNLinking>0724-8741</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Antibodies, Monoclonal, Humanized</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Antineoplastic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Chelating Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Dendrimers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Indium Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Nylons</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>PAMAM-G4</NameOfSubstance></Chemical><Chemical><RegistryNumber>7A314HQM0I</RegistryNumber><NameOfSubstance>Pentetic Acid</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance>Receptor, erbB-2</NameOfSubstance></Chemical><Chemical><RegistryNumber>P188ANX8CK</RegistryNumber><NameOfSubstance>trastuzumab</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Antibodies, Monoclonal, Humanized</DescriptorName><QualifierName MajorTopicYN="Y">chemistry</QualifierName><QualifierName MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Antineoplastic Agents</DescriptorName><QualifierName MajorTopicYN="Y">chemistry</QualifierName><QualifierName MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Breast Neoplasms</DescriptorName><QualifierName MajorTopicYN="N">drug therapy</QualifierName><QualifierName MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Cell Survival</DescriptorName><QualifierName MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Chelating Agents</DescriptorName><QualifierName MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Dendrimers</DescriptorName><QualifierName MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Indium Radioisotopes</DescriptorName><QualifierName MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Nylons</DescriptorName><QualifierName MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Pentetic Acid</DescriptorName><QualifierName MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Receptor, erbB-2</DescriptorName><QualifierName MajorTopicYN="Y">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2013</Year><Month>1</Month><Day>5</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2013</Year><Month>4</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="aheadofprint"><Year>2013</Year><Month>4</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>4</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>4</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>1</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1007/s11095-013-1044-1</ArticleId><ArticleId IdType="pubmed">23615858</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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