Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET.
Identifieur interne : 003712 ( Main/Exploration ); précédent : 003711; suivant : 003713Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET.
Auteurs : RBID : pubmed:11578904English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (diagnostic use), Antibodies, Monoclonal (pharmacokinetics), Chelating Agents (diagnostic use), Female, Gallium (chemistry), Indicators and Reagents, Indium Radioisotopes (diagnostic use), Iodine Radioisotopes (diagnostic use), Isotope Labeling, Mammary Neoplasms, Experimental (radionuclide imaging), Mice, Mice, Nude, Mucin-1 (immunology), Mucins (immunology), Neoplasm Transplantation, Radiopharmaceuticals (diagnostic use), Radiopharmaceuticals (pharmacokinetics), Technetium (diagnostic use), Tissue Distribution, Tomography, Emission-Computed.
- MESH :
- chemical , chemistry : Gallium.
- chemical , diagnostic use : Antibodies, Monoclonal, Chelating Agents, Indium Radioisotopes, Iodine Radioisotopes, Radiopharmaceuticals, Technetium.
- chemical , immunology : Mucin-1, Mucins.
- chemical , pharmacokinetics : Antibodies, Monoclonal, Radiopharmaceuticals.
- radionuclide imaging : Mammary Neoplasms, Experimental.
- Animals, Female, Indicators and Reagents, Isotope Labeling, Mice, Mice, Nude, Neoplasm Transplantation, Tissue Distribution, Tomography, Emission-Computed.
Abstract
We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter 68Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab')(2) fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10(7) M(-1)) while the binding capacity of cells was high (8.4 x 10(6) BS-MAbs per cell). Tumor uptake of the 67Ga labeled chelate in pretargeted animals was to 5.8 +/- 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with 125I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the 68Ga and 67Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the 68Ga chelate, clearly visualized all tumors.
PubMed: 11578904
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET.</title><author><name sortKey="Schuhmacher, J" uniqKey="Schuhmacher J">J Schuhmacher</name><affiliation wicri:level="3"><nlm:affiliation>Department of Diagnostic and Therapeutic Radiology German Cancer Research Center, Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Diagnostic and Therapeutic Radiology German Cancer Research Center, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Klivenyi, G" uniqKey="Klivenyi G">G Klivényi</name></author><author><name sortKey="Kaul, S" uniqKey="Kaul S">S Kaul</name></author><author><name sortKey="Henze, M" uniqKey="Henze M">M Henze</name></author><author><name sortKey="Matys, R" uniqKey="Matys R">R Matys</name></author><author><name sortKey="Hauser, H" uniqKey="Hauser H">H Hauser</name></author><author><name sortKey="Clorius, J" uniqKey="Clorius J">J Clorius</name></author></titleStmt><publicationStmt><date when="2001">2001</date><idno type="RBID">pubmed:11578904</idno><idno type="pmid">11578904</idno><idno type="wicri:Area/Main/Corpus">003919</idno><idno type="wicri:Area/Main/Curation">003919</idno><idno type="wicri:Area/Main/Exploration">003712</idno></publicationStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Monoclonal (diagnostic use)</term><term>Antibodies, Monoclonal (pharmacokinetics)</term><term>Chelating Agents (diagnostic use)</term><term>Female</term><term>Gallium (chemistry)</term><term>Indicators and Reagents</term><term>Indium Radioisotopes (diagnostic use)</term><term>Iodine Radioisotopes (diagnostic use)</term><term>Isotope Labeling</term><term>Mammary Neoplasms, Experimental (radionuclide imaging)</term><term>Mice</term><term>Mice, Nude</term><term>Mucin-1 (immunology)</term><term>Mucins (immunology)</term><term>Neoplasm Transplantation</term><term>Radiopharmaceuticals (diagnostic use)</term><term>Radiopharmaceuticals (pharmacokinetics)</term><term>Technetium (diagnostic use)</term><term>Tissue Distribution</term><term>Tomography, Emission-Computed</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Gallium</term></keywords><keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Chelating Agents</term><term>Indium Radioisotopes</term><term>Iodine Radioisotopes</term><term>Radiopharmaceuticals</term><term>Technetium</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Mucin-1</term><term>Mucins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Radiopharmaceuticals</term></keywords><keywords scheme="MESH" qualifier="radionuclide imaging" xml:lang="en"><term>Mammary Neoplasms, Experimental</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Indicators and Reagents</term><term>Isotope Labeling</term><term>Mice</term><term>Mice, Nude</term><term>Neoplasm Transplantation</term><term>Tissue Distribution</term><term>Tomography, Emission-Computed</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter 68Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab')(2) fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10(7) M(-1)) while the binding capacity of cells was high (8.4 x 10(6) BS-MAbs per cell). Tumor uptake of the 67Ga labeled chelate in pretargeted animals was to 5.8 +/- 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with 125I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the 68Ga and 67Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the 68Ga chelate, clearly visualized all tumors.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">11578904</PMID><DateCreated><Year>2001</Year><Month>10</Month><Day>01</Day></DateCreated><DateCompleted><Year>2002</Year><Month>01</Month><Day>22</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0969-8051</ISSN><JournalIssue CitedMedium="Print"><Volume>28</Volume><Issue>7</Issue><PubDate><Year>2001</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Nuclear medicine and biology</Title><ISOAbbreviation>Nucl. Med. Biol.</ISOAbbreviation></Journal><ArticleTitle>Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET.</ArticleTitle><Pagination><MedlinePgn>821-8</MedlinePgn></Pagination><Abstract><AbstractText>We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter 68Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab')(2) fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10(7) M(-1)) while the binding capacity of cells was high (8.4 x 10(6) BS-MAbs per cell). Tumor uptake of the 67Ga labeled chelate in pretargeted animals was to 5.8 +/- 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with 125I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the 68Ga and 67Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the 68Ga chelate, clearly visualized all tumors.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Schuhmacher</LastName><ForeName>J</ForeName><Initials>J</Initials><Affiliation>Department of Diagnostic and Therapeutic Radiology German Cancer Research Center, Heidelberg, Germany.</Affiliation></Author><Author ValidYN="Y"><LastName>Klivényi</LastName><ForeName>G</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Kaul</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Henze</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Matys</LastName><ForeName>R</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Hauser</LastName><ForeName>H</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Clorius</LastName><ForeName>J</ForeName><Initials>J</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nucl Med Biol</MedlineTA><NlmUniqueID>9304420</NlmUniqueID><ISSNLinking>0969-8051</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Antibodies, Monoclonal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Chelating Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Indicators and Reagents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Indium Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Iodine Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Mucin-1</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Mucins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Radiopharmaceuticals</NameOfSubstance></Chemical><Chemical><RegistryNumber>7440-26-8</RegistryNumber><NameOfSubstance>Technetium</NameOfSubstance></Chemical><Chemical><RegistryNumber>CH46OC8YV4</RegistryNumber><NameOfSubstance>Gallium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Antibodies, Monoclonal</DescriptorName><QualifierName MajorTopicYN="Y">diagnostic use</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Chelating Agents</DescriptorName><QualifierName MajorTopicYN="Y">diagnostic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Gallium</DescriptorName><QualifierName MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Indicators and Reagents</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Indium Radioisotopes</DescriptorName><QualifierName MajorTopicYN="N">diagnostic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Iodine Radioisotopes</DescriptorName><QualifierName MajorTopicYN="N">diagnostic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Isotope Labeling</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mammary Neoplasms, Experimental</DescriptorName><QualifierName MajorTopicYN="Y">radionuclide imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice, Nude</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mucin-1</DescriptorName><QualifierName MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mucins</DescriptorName><QualifierName MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Neoplasm Transplantation</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Radiopharmaceuticals</DescriptorName><QualifierName MajorTopicYN="Y">diagnostic use</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Technetium</DescriptorName><QualifierName MajorTopicYN="N">diagnostic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Tissue Distribution</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Tomography, Emission-Computed</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2001</Year><Month>10</Month><Day>2</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2002</Year><Month>1</Month><Day>23</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2001</Year><Month>10</Month><Day>2</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11578904</ArticleId><ArticleId IdType="pii">S0969-8051(01)00246-3</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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