Toxicity and efficacy of radioimmunotherapy in carcinoembryonic antigen-producing medullary thyroid cancer xenograft: comparison of iodine 131-labeled F(ab')2 and pretargeted bivalent hapten and evaluation of repeated injections.
Identifieur interne : 003B25 ( Main/Exploration ); précédent : 003B24; suivant : 003B26Toxicity and efficacy of radioimmunotherapy in carcinoembryonic antigen-producing medullary thyroid cancer xenograft: comparison of iodine 131-labeled F(ab')2 and pretargeted bivalent hapten and evaluation of repeated injections.
Auteurs : RBID : pubmed:10541362English descriptors
- KwdEn :
- Animals, Carcinoembryonic Antigen (analysis), Carcinoembryonic Antigen (immunology), Carcinoma, Medullary (pathology), Carcinoma, Medullary (radiotherapy), Haptens (therapeutic use), Humans, Immunoglobulin Fab Fragments (therapeutic use), Injections, Iodine Radioisotopes (therapeutic use), Mice, Mice, Nude, Neoplasm Transplantation, Pentetic Acid, Radioimmunotherapy (adverse effects), Thyroid Neoplasms (pathology), Thyroid Neoplasms (radiotherapy), Transplantation, Heterologous, Tumor Cells, Cultured.
- MESH :
- chemical , analysis : Carcinoembryonic Antigen.
- chemical , immunology : Carcinoembryonic Antigen.
- adverse effects : Radioimmunotherapy.
- pathology : Carcinoma, Medullary, Thyroid Neoplasms.
- radiotherapy : Carcinoma, Medullary, Thyroid Neoplasms.
- chemical , therapeutic use : Haptens, Immunoglobulin Fab Fragments, Iodine Radioisotopes.
- Animals, Humans, Injections, Mice, Mice, Nude, Neoplasm Transplantation, Pentetic Acid, Transplantation, Heterologous, Tumor Cells, Cultured.
Abstract
This study compared the toxicity and efficacy of 131I-labeled bivalent hapten pretargeted by anti-carcinoembryonic antigen (CEA)/anti-N alpha-(diethylenetriamine-N,N,N',N''-tetraacetic acid-indium(F6-734) bispecific antibody [affinity enhancement system (AES) reagents] with 131I-labeled anti-CEA F(ab')2 (131I-F6) in mice grafted with a human medullary thyroid carcinoma. Repeated injections of AES reagents were also evaluated. Mice bearing TT tumor xenografts were treated with 37, 74, or 92.5 MBq of AES reagents, two injections of 74 MBq of AES reagents 45 days apart, or 37 or 92.5 MBq of 131I-F6. Control groups were treated with nonspecific 131I-labeled F(ab')2, nonspecific AES reagents, nonradiolabeled F6, F6-734 bispecific antibody, and nonradiolabeled bivalent hapten or received no injection. For AES treatments, bispecific antibody was injected 48 h before the hapten. Animal weight, hematological toxicity, tumor volume, and serum thyrocalcitonin were monitored during 5 months. At 92.5 MBq, weight loss was significantly lower after AES than F6 treatment (P = 0.004). The percentages of leukocyte count changes were significantly lower after AES than F6 at 37 and 92.5 MBq (P = 0.01 and 0.04, respectively). The percentage of platelet count changes was significantly lower with AES at the 92.5-MBq dose level (P = 0.04). In the group injected twice with AES reagents, toxicity was not significantly increased after the second treatment. Tumor response was observed in all cases but was significantly longer with repeated treatments of 74 MBq AES reagents than with a single treatment (P = 0.004). Two complete responses were observed with repeated treatments. Changes in thyrocacitonin level paralleled those in tumor volume. These results indicate that pretargeted radioimmunotherapy was at least as efficient as one-step radioimmunotherapy and markedly less toxic. Repeated treatments with AES reagents increased efficacy without increasing toxicity.
PubMed: 10541362
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Toxicity and efficacy of radioimmunotherapy in carcinoembryonic antigen-producing medullary thyroid cancer xenograft: comparison of iodine 131-labeled F(ab')2 and pretargeted bivalent hapten and evaluation of repeated injections.</title><author><name sortKey="Kraeber Bodere, F" uniqKey="Kraeber Bodere F">F Kraeber-Bodéré</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, Research Unit 463, Nantes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Research Unit 463, Nantes</wicri:regionArea><placeName><region type="région">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Faivre Chauvet, A" uniqKey="Faivre Chauvet A">A Faivre-Chauvet</name></author><author><name sortKey="Sai Maurel, C" uniqKey="Sai Maurel C">C Saï-Maurel</name></author><author><name sortKey="Campion, L" uniqKey="Campion L">L Campion</name></author><author><name sortKey="Fiche, M" uniqKey="Fiche M">M Fiche</name></author><author><name sortKey="Gautherot, E" uniqKey="Gautherot E">E Gautherot</name></author><author><name sortKey="Le Boterff, J" uniqKey="Le Boterff J">J Le Boterff</name></author><author><name sortKey="Barbet, J" uniqKey="Barbet J">J Barbet</name></author><author><name sortKey="Chatal, J F" uniqKey="Chatal J">J F Chatal</name></author><author><name sortKey="Thedrez, P" uniqKey="Thedrez P">P Thédrez</name></author></titleStmt><publicationStmt><date when="1999">1999</date><idno type="RBID">pubmed:10541362</idno><idno type="pmid">10541362</idno><idno type="wicri:Area/Main/Corpus">003E03</idno><idno type="wicri:Area/Main/Curation">003E03</idno><idno type="wicri:Area/Main/Exploration">003B25</idno></publicationStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Carcinoembryonic Antigen (analysis)</term><term>Carcinoembryonic Antigen (immunology)</term><term>Carcinoma, Medullary (pathology)</term><term>Carcinoma, Medullary (radiotherapy)</term><term>Haptens (therapeutic use)</term><term>Humans</term><term>Immunoglobulin Fab Fragments (therapeutic use)</term><term>Injections</term><term>Iodine Radioisotopes (therapeutic use)</term><term>Mice</term><term>Mice, Nude</term><term>Neoplasm Transplantation</term><term>Pentetic Acid</term><term>Radioimmunotherapy (adverse effects)</term><term>Thyroid Neoplasms (pathology)</term><term>Thyroid Neoplasms (radiotherapy)</term><term>Transplantation, Heterologous</term><term>Tumor Cells, Cultured</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Carcinoembryonic Antigen</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Carcinoembryonic Antigen</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Radioimmunotherapy</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Carcinoma, Medullary</term><term>Thyroid Neoplasms</term></keywords><keywords scheme="MESH" qualifier="radiotherapy" xml:lang="en"><term>Carcinoma, Medullary</term><term>Thyroid Neoplasms</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Haptens</term><term>Immunoglobulin Fab Fragments</term><term>Iodine Radioisotopes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Injections</term><term>Mice</term><term>Mice, Nude</term><term>Neoplasm Transplantation</term><term>Pentetic Acid</term><term>Transplantation, Heterologous</term><term>Tumor Cells, Cultured</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">This study compared the toxicity and efficacy of 131I-labeled bivalent hapten pretargeted by anti-carcinoembryonic antigen (CEA)/anti-N alpha-(diethylenetriamine-N,N,N',N''-tetraacetic acid-indium(F6-734) bispecific antibody [affinity enhancement system (AES) reagents] with 131I-labeled anti-CEA F(ab')2 (131I-F6) in mice grafted with a human medullary thyroid carcinoma. Repeated injections of AES reagents were also evaluated. Mice bearing TT tumor xenografts were treated with 37, 74, or 92.5 MBq of AES reagents, two injections of 74 MBq of AES reagents 45 days apart, or 37 or 92.5 MBq of 131I-F6. Control groups were treated with nonspecific 131I-labeled F(ab')2, nonspecific AES reagents, nonradiolabeled F6, F6-734 bispecific antibody, and nonradiolabeled bivalent hapten or received no injection. For AES treatments, bispecific antibody was injected 48 h before the hapten. Animal weight, hematological toxicity, tumor volume, and serum thyrocalcitonin were monitored during 5 months. At 92.5 MBq, weight loss was significantly lower after AES than F6 treatment (P = 0.004). The percentages of leukocyte count changes were significantly lower after AES than F6 at 37 and 92.5 MBq (P = 0.01 and 0.04, respectively). The percentage of platelet count changes was significantly lower with AES at the 92.5-MBq dose level (P = 0.04). In the group injected twice with AES reagents, toxicity was not significantly increased after the second treatment. Tumor response was observed in all cases but was significantly longer with repeated treatments of 74 MBq AES reagents than with a single treatment (P = 0.004). Two complete responses were observed with repeated treatments. Changes in thyrocacitonin level paralleled those in tumor volume. These results indicate that pretargeted radioimmunotherapy was at least as efficient as one-step radioimmunotherapy and markedly less toxic. Repeated treatments with AES reagents increased efficacy without increasing toxicity.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">10541362</PMID><DateCreated><Year>1999</Year><Month>11</Month><Day>24</Day></DateCreated><DateCompleted><Year>1999</Year><Month>11</Month><Day>24</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1078-0432</ISSN><JournalIssue CitedMedium="Print"><Volume>5</Volume><Issue>10 Suppl</Issue><PubDate><Year>1999</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Clinical cancer research : an official journal of the American Association for Cancer Research</Title><ISOAbbreviation>Clin. Cancer Res.</ISOAbbreviation></Journal><ArticleTitle>Toxicity and efficacy of radioimmunotherapy in carcinoembryonic antigen-producing medullary thyroid cancer xenograft: comparison of iodine 131-labeled F(ab')2 and pretargeted bivalent hapten and evaluation of repeated injections.</ArticleTitle><Pagination><MedlinePgn>3183s-3189s</MedlinePgn></Pagination><Abstract><AbstractText>This study compared the toxicity and efficacy of 131I-labeled bivalent hapten pretargeted by anti-carcinoembryonic antigen (CEA)/anti-N alpha-(diethylenetriamine-N,N,N',N''-tetraacetic acid-indium(F6-734) bispecific antibody [affinity enhancement system (AES) reagents] with 131I-labeled anti-CEA F(ab')2 (131I-F6) in mice grafted with a human medullary thyroid carcinoma. Repeated injections of AES reagents were also evaluated. Mice bearing TT tumor xenografts were treated with 37, 74, or 92.5 MBq of AES reagents, two injections of 74 MBq of AES reagents 45 days apart, or 37 or 92.5 MBq of 131I-F6. Control groups were treated with nonspecific 131I-labeled F(ab')2, nonspecific AES reagents, nonradiolabeled F6, F6-734 bispecific antibody, and nonradiolabeled bivalent hapten or received no injection. For AES treatments, bispecific antibody was injected 48 h before the hapten. Animal weight, hematological toxicity, tumor volume, and serum thyrocalcitonin were monitored during 5 months. At 92.5 MBq, weight loss was significantly lower after AES than F6 treatment (P = 0.004). The percentages of leukocyte count changes were significantly lower after AES than F6 at 37 and 92.5 MBq (P = 0.01 and 0.04, respectively). The percentage of platelet count changes was significantly lower with AES at the 92.5-MBq dose level (P = 0.04). In the group injected twice with AES reagents, toxicity was not significantly increased after the second treatment. Tumor response was observed in all cases but was significantly longer with repeated treatments of 74 MBq AES reagents than with a single treatment (P = 0.004). Two complete responses were observed with repeated treatments. Changes in thyrocacitonin level paralleled those in tumor volume. These results indicate that pretargeted radioimmunotherapy was at least as efficient as one-step radioimmunotherapy and markedly less toxic. Repeated treatments with AES reagents increased efficacy without increasing toxicity.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kraeber-Bodéré</LastName><ForeName>F</ForeName><Initials>F</Initials><Affiliation>Institut National de la Santé et de la Recherche Médicale, Research Unit 463, Nantes, France.</Affiliation></Author><Author ValidYN="Y"><LastName>Faivre-Chauvet</LastName><ForeName>A</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Saï-Maurel</LastName><ForeName>C</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Campion</LastName><ForeName>L</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Fiche</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Gautherot</LastName><ForeName>E</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Le Boterff</LastName><ForeName>J</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Barbet</LastName><ForeName>J</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Chatal</LastName><ForeName>J F</ForeName><Initials>JF</Initials></Author><Author ValidYN="Y"><LastName>Thédrez</LastName><ForeName>P</ForeName><Initials>P</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Comparative Study</PublicationType><PublicationType>Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>UNITED STATES</Country><MedlineTA>Clin Cancer Res</MedlineTA><NlmUniqueID>9502500</NlmUniqueID><ISSNLinking>1078-0432</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Carcinoembryonic Antigen</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Haptens</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Immunoglobulin Fab Fragments</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Iodine Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>7A314HQM0I</RegistryNumber><NameOfSubstance>Pentetic Acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Carcinoembryonic Antigen</DescriptorName><QualifierName MajorTopicYN="Y">analysis</QualifierName><QualifierName MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Carcinoma, Medullary</DescriptorName><QualifierName MajorTopicYN="N">pathology</QualifierName><QualifierName MajorTopicYN="Y">radiotherapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Haptens</DescriptorName><QualifierName MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Immunoglobulin Fab Fragments</DescriptorName><QualifierName MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Injections</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Iodine Radioisotopes</DescriptorName><QualifierName MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice, Nude</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Neoplasm Transplantation</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Pentetic Acid</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Radioimmunotherapy</DescriptorName><QualifierName 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IdType="pubmed">10541362</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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