Pre-clinical and clinical studies of two new bifunctional chelating agents for immunoscintigraphy with 111In-anti-CEA monoclonal antibody.
Identifieur interne : 004343 ( Main/Exploration ); précédent : 004342; suivant : 004344Pre-clinical and clinical studies of two new bifunctional chelating agents for immunoscintigraphy with 111In-anti-CEA monoclonal antibody.
Auteurs : RBID : pubmed:8895905English descriptors
- KwdEn :
- Adenocarcinoma (radionuclide imaging), Adenocarcinoma (secondary), Animals, Antibodies, Bispecific (diagnostic use), Antibodies, Bispecific (isolation & purification), Antibodies, Bispecific (pharmacokinetics), Antibodies, Monoclonal (diagnostic use), Antibodies, Monoclonal (isolation & purification), Antibodies, Monoclonal (pharmacokinetics), Carcinoembryonic Antigen (immunology), Chelating Agents, Colorectal Neoplasms (radionuclide imaging), Edetic Acid (analogs & derivatives), Female, Guinea Pigs, Humans, Indium Radioisotopes (diagnostic use), Indium Radioisotopes (pharmacokinetics), Male, Mice, Mice, Nude, Neoplasm Recurrence, Local (radionuclide imaging), Pentetic Acid (analogs & derivatives), Radioimmunodetection (methods).
- MESH :
- chemical , analogs & derivatives : Edetic Acid, Pentetic Acid.
- chemical , diagnostic use : Antibodies, Bispecific, Antibodies, Monoclonal, Indium Radioisotopes.
- chemical , immunology : Carcinoembryonic Antigen.
- chemical , isolation & purification : Antibodies, Bispecific, Antibodies, Monoclonal.
- chemical , pharmacokinetics : Antibodies, Bispecific, Antibodies, Monoclonal, Indium Radioisotopes.
- methods : Radioimmunodetection.
- radionuclide imaging : Adenocarcinoma, Colorectal Neoplasms, Neoplasm Recurrence, Local.
- secondary : Adenocarcinoma.
- Animals, Chelating Agents, Female, Guinea Pigs, Humans, Male, Mice, Mice, Nude.
Abstract
Anti-CEA F(ab')2 monoclonal antibody fragments [F6 MAb F(ab')2] were conjugated to two bifunctional semi-rigid chelating agents derived from trans-1,2-diaminocyclohexane tetraacetic acid (CDTA), the monolithium salt of N-[methyl(2-isothiocyanatoethyl)carbamide] trans-1,2-diaminocyclohexane-N,N',N'-triacetic acid (SCN), and 4 isothiocyanato-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (4-ICE) and labelled with 111In to obtain IIIIn-labelled-F6 MAb F(ab')2 conjugates (111In-F6-SCN and 111In-F6-4-ICE respectively). Biodistribution in mice and clinical studies were undertaken to assess the potential of these two ligands in the detection of colorectal adenocarcinoma recurrences and metastases in humans. Toxicity studies were carried out on guinea pigs and Swiss mice injected with a dose proportionally 100 times greater than that used in human studies. Clinical studies were performed in patients with clinically and/or biologically suspected adenocarcinoma recurrences. No immunoconjugate-induced toxicity was found. The biodistribution studies in mice gave better visualization of tumour sites with 111In-F6-SCN and 111In-F6-4-ICE than with 111In-F6-DTPA. Ten patients were included in the clinical protocol. 111In-F6-SCN and 111In-F6-4-ICE effectively visualized adenocarcinoma recurrences. However, in this small series, 111In-F6-4-ICE performed somewhat better than 111In-F6-SCN. The present study has demonstrated the potential of new bifunctional semi-rigid chelating agents coupled to antibody and labelled with 111In to localize recurrences (especially in liver) in humans using a one-step targeting method.
PubMed: 8895905
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Pre-clinical and clinical studies of two new bifunctional chelating agents for immunoscintigraphy with 111In-anti-CEA monoclonal antibody.</title><author><name sortKey="Faivre Chauvet, A" uniqKey="Faivre Chauvet A">A Faivre-Chauvet</name><affiliation wicri:level="1"><nlm:affiliation>INSERM Research Unit 211, Nantes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM Research Unit 211, Nantes</wicri:regionArea><placeName><region type="région">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Mease, R C" uniqKey="Mease R">R C Mease</name></author><author><name sortKey="Chetanneau, A" uniqKey="Chetanneau A">A Chetanneau</name></author><author><name sortKey="Bardies, M" uniqKey="Bardies M">M Bardiès</name></author><author><name sortKey="Sai Maurel, C" uniqKey="Sai Maurel C">C Sai-Maurel</name></author><author><name sortKey="Meinken, G E" uniqKey="Meinken G">G E Meinken</name></author><author><name sortKey="Srivastava, S C" uniqKey="Srivastava S">S C Srivastava</name></author><author><name sortKey="Chatal, J F" uniqKey="Chatal J">J F Chatal</name></author><author><name sortKey="Gestin, J F" uniqKey="Gestin J">J F Gestin</name></author></titleStmt><publicationStmt><date when="1996">1996</date><idno type="RBID">pubmed:8895905</idno><idno type="pmid">8895905</idno><idno type="wicri:Area/Main/Corpus">004554</idno><idno type="wicri:Area/Main/Curation">004554</idno><idno type="wicri:Area/Main/Exploration">004343</idno></publicationStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenocarcinoma (radionuclide imaging)</term><term>Adenocarcinoma (secondary)</term><term>Animals</term><term>Antibodies, Bispecific (diagnostic use)</term><term>Antibodies, Bispecific (isolation & purification)</term><term>Antibodies, Bispecific (pharmacokinetics)</term><term>Antibodies, Monoclonal (diagnostic use)</term><term>Antibodies, Monoclonal (isolation & purification)</term><term>Antibodies, Monoclonal (pharmacokinetics)</term><term>Carcinoembryonic Antigen (immunology)</term><term>Chelating Agents</term><term>Colorectal Neoplasms (radionuclide imaging)</term><term>Edetic Acid (analogs & derivatives)</term><term>Female</term><term>Guinea Pigs</term><term>Humans</term><term>Indium Radioisotopes (diagnostic use)</term><term>Indium Radioisotopes (pharmacokinetics)</term><term>Male</term><term>Mice</term><term>Mice, Nude</term><term>Neoplasm Recurrence, Local (radionuclide imaging)</term><term>Pentetic Acid (analogs & derivatives)</term><term>Radioimmunodetection (methods)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Edetic Acid</term><term>Pentetic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Antibodies, Bispecific</term><term>Antibodies, Monoclonal</term><term>Indium Radioisotopes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Carcinoembryonic Antigen</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Antibodies, Bispecific</term><term>Antibodies, Monoclonal</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antibodies, Bispecific</term><term>Antibodies, Monoclonal</term><term>Indium Radioisotopes</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Radioimmunodetection</term></keywords><keywords scheme="MESH" qualifier="radionuclide imaging" xml:lang="en"><term>Adenocarcinoma</term><term>Colorectal Neoplasms</term><term>Neoplasm Recurrence, Local</term></keywords><keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Adenocarcinoma</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chelating Agents</term><term>Female</term><term>Guinea Pigs</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Nude</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Anti-CEA F(ab')2 monoclonal antibody fragments [F6 MAb F(ab')2] were conjugated to two bifunctional semi-rigid chelating agents derived from trans-1,2-diaminocyclohexane tetraacetic acid (CDTA), the monolithium salt of N-[methyl(2-isothiocyanatoethyl)carbamide] trans-1,2-diaminocyclohexane-N,N',N'-triacetic acid (SCN), and 4 isothiocyanato-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (4-ICE) and labelled with 111In to obtain IIIIn-labelled-F6 MAb F(ab')2 conjugates (111In-F6-SCN and 111In-F6-4-ICE respectively). Biodistribution in mice and clinical studies were undertaken to assess the potential of these two ligands in the detection of colorectal adenocarcinoma recurrences and metastases in humans. Toxicity studies were carried out on guinea pigs and Swiss mice injected with a dose proportionally 100 times greater than that used in human studies. Clinical studies were performed in patients with clinically and/or biologically suspected adenocarcinoma recurrences. No immunoconjugate-induced toxicity was found. The biodistribution studies in mice gave better visualization of tumour sites with 111In-F6-SCN and 111In-F6-4-ICE than with 111In-F6-DTPA. Ten patients were included in the clinical protocol. 111In-F6-SCN and 111In-F6-4-ICE effectively visualized adenocarcinoma recurrences. However, in this small series, 111In-F6-4-ICE performed somewhat better than 111In-F6-SCN. The present study has demonstrated the potential of new bifunctional semi-rigid chelating agents coupled to antibody and labelled with 111In to localize recurrences (especially in liver) in humans using a one-step targeting method.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">8895905</PMID><DateCreated><Year>1997</Year><Month>03</Month><Day>10</Day></DateCreated><DateCompleted><Year>1997</Year><Month>03</Month><Day>10</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0143-3636</ISSN><JournalIssue CitedMedium="Print"><Volume>17</Volume><Issue>9</Issue><PubDate><Year>1996</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Nuclear medicine communications</Title><ISOAbbreviation>Nucl Med Commun</ISOAbbreviation></Journal><ArticleTitle>Pre-clinical and clinical studies of two new bifunctional chelating agents for immunoscintigraphy with 111In-anti-CEA monoclonal antibody.</ArticleTitle><Pagination><MedlinePgn>781-9</MedlinePgn></Pagination><Abstract><AbstractText>Anti-CEA F(ab')2 monoclonal antibody fragments [F6 MAb F(ab')2] were conjugated to two bifunctional semi-rigid chelating agents derived from trans-1,2-diaminocyclohexane tetraacetic acid (CDTA), the monolithium salt of N-[methyl(2-isothiocyanatoethyl)carbamide] trans-1,2-diaminocyclohexane-N,N',N'-triacetic acid (SCN), and 4 isothiocyanato-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (4-ICE) and labelled with 111In to obtain IIIIn-labelled-F6 MAb F(ab')2 conjugates (111In-F6-SCN and 111In-F6-4-ICE respectively). Biodistribution in mice and clinical studies were undertaken to assess the potential of these two ligands in the detection of colorectal adenocarcinoma recurrences and metastases in humans. Toxicity studies were carried out on guinea pigs and Swiss mice injected with a dose proportionally 100 times greater than that used in human studies. Clinical studies were performed in patients with clinically and/or biologically suspected adenocarcinoma recurrences. No immunoconjugate-induced toxicity was found. The biodistribution studies in mice gave better visualization of tumour sites with 111In-F6-SCN and 111In-F6-4-ICE than with 111In-F6-DTPA. Ten patients were included in the clinical protocol. 111In-F6-SCN and 111In-F6-4-ICE effectively visualized adenocarcinoma recurrences. However, in this small series, 111In-F6-4-ICE performed somewhat better than 111In-F6-SCN. The present study has demonstrated the potential of new bifunctional semi-rigid chelating agents coupled to antibody and labelled with 111In to localize recurrences (especially in liver) in humans using a one-step targeting method.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Faivre-Chauvet</LastName><ForeName>A</ForeName><Initials>A</Initials><Affiliation>INSERM Research Unit 211, Nantes, France.</Affiliation></Author><Author ValidYN="Y"><LastName>Mease</LastName><ForeName>R C</ForeName><Initials>RC</Initials></Author><Author ValidYN="Y"><LastName>Chetanneau</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Bardiès</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Sai-Maurel</LastName><ForeName>C</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Meinken</LastName><ForeName>G E</ForeName><Initials>GE</Initials></Author><Author ValidYN="Y"><LastName>Srivastava</LastName><ForeName>S C</ForeName><Initials>SC</Initials></Author><Author ValidYN="Y"><LastName>Chatal</LastName><ForeName>J F</ForeName><Initials>JF</Initials></Author><Author ValidYN="Y"><LastName>Gestin</LastName><ForeName>J F</ForeName><Initials>JF</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType><PublicationType>Research Support, Non-U.S. Gov't</PublicationType><PublicationType>Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>ENGLAND</Country><MedlineTA>Nucl Med Commun</MedlineTA><NlmUniqueID>8201017</NlmUniqueID><ISSNLinking>0143-3636</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Antibodies, Bispecific</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Antibodies, Monoclonal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Carcinoembryonic Antigen</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Chelating Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Indium Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>482-54-2</RegistryNumber><NameOfSubstance>CDTA</NameOfSubstance></Chemical><Chemical><RegistryNumber>7A314HQM0I</RegistryNumber><NameOfSubstance>Pentetic Acid</NameOfSubstance></Chemical><Chemical><RegistryNumber>9G34HU7RV0</RegistryNumber><NameOfSubstance>Edetic Acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Adenocarcinoma</DescriptorName><QualifierName MajorTopicYN="N">radionuclide imaging</QualifierName><QualifierName MajorTopicYN="N">secondary</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Antibodies, Bispecific</DescriptorName><QualifierName MajorTopicYN="Y">diagnostic use</QualifierName><QualifierName MajorTopicYN="N">isolation & purification</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Antibodies, Monoclonal</DescriptorName><QualifierName MajorTopicYN="Y">diagnostic use</QualifierName><QualifierName MajorTopicYN="N">isolation & purification</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Carcinoembryonic Antigen</DescriptorName><QualifierName MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y">Chelating Agents</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Colorectal Neoplasms</DescriptorName><QualifierName MajorTopicYN="N">radionuclide imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Edetic Acid</DescriptorName><QualifierName MajorTopicYN="N">analogs & derivatives</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Guinea Pigs</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Indium Radioisotopes</DescriptorName><QualifierName MajorTopicYN="N">diagnostic use</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice, Nude</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Neoplasm Recurrence, Local</DescriptorName><QualifierName MajorTopicYN="N">radionuclide imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Pentetic Acid</DescriptorName><QualifierName MajorTopicYN="N">analogs & derivatives</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Radioimmunodetection</DescriptorName><QualifierName MajorTopicYN="Y">methods</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1996</Year><Month>9</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1996</Year><Month>9</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate 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