Preclinical evaluation of monoclonal antibody 14C5 for targeting pancreatic cancer.
Identifieur interne : 001809 ( Main/Exploration ); précédent : 001808; suivant : 001810Preclinical evaluation of monoclonal antibody 14C5 for targeting pancreatic cancer.
Auteurs : RBID : pubmed:20423233English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (pharmacokinetics), Antibodies, Monoclonal (therapeutic use), Drug Evaluation, Preclinical, Female, Humans, Iodine Radioisotopes (diagnostic use), Mice, Mice, Nude, Pancreas (immunology), Pancreas (metabolism), Pancreas (pathology), Pancreatic Neoplasms (immunology), Pancreatic Neoplasms (metabolism), Pancreatic Neoplasms (therapy), Pentetic Acid (analogs & derivatives), Pentetic Acid (pharmacokinetics), Radioimmunoassay, Radiopharmaceuticals (diagnostic use), Receptors, Vitronectin (immunology), Receptors, Vitronectin (metabolism), Tissue Distribution, Tumor Cells, Cultured, Xenograft Model Antitumor Assays.
- MESH :
- chemical , analogs & derivatives : Pentetic Acid.
- chemical , diagnostic use : Iodine Radioisotopes, Radiopharmaceuticals.
- chemical , immunology : Receptors, Vitronectin.
- chemical , metabolism : Receptors, Vitronectin.
- chemical , pharmacokinetics : Antibodies, Monoclonal, Pentetic Acid.
- chemical , therapeutic use : Antibodies, Monoclonal.
- immunology : Pancreas, Pancreatic Neoplasms.
- metabolism : Pancreas, Pancreatic Neoplasms.
- pathology : Pancreas.
- therapy : Pancreatic Neoplasms.
- Animals, Drug Evaluation, Preclinical, Female, Humans, Mice, Mice, Nude, Radioimmunoassay, Tissue Distribution, Tumor Cells, Cultured, Xenograft Model Antitumor Assays.
Abstract
The use of radiolabeled antibodies that are able to target primary tumors as well as metastatic tumor sites with minimal reactivity to normal tissues is a promising approach for treating pancreatic cancer. In this study, the integrin alpha(v)beta(5) is studied as a target for the diagnosis of and potential therapy for human pancreatic cancer by using the radiolabeled murine monoclonal antibody (mAb) 14C5. Biopsy specimens from human pancreatic tumors were examined for the expression of the integrin alpha(v)beta(5). The pancreatic tumor cell line Capan-1 was used to test the in vitro targeting potency of mAb 14C5 labeled with 125/131-iodine and 111-indium. Internalization, retention, and metabolism were investigated in cellular radioimmunoassays. Biodistribution and tumor-targeting characteristics were studied in Capan-1 xenografts. All tumor sections were positive for the integrin alpha(v)beta(5), with an extensive positive staining of the stroma. Saturation binding experiments showed high affinity with comparable K(d)s. In vitro internalization experiments showed a longer intracellular retention of (111)In-p-benzyl isothiocyanate-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA)-14C5 in comparison to (125)I-14C5 and (111)In-p-isothiocyanatobenzyl diethylenetriaminepentaacetic acid (p-SCN-Bz-DTPA)-14C5. In vivo radioisotope tumor uptake was maximum at 48-72 hours, with the uptake of (111)In-p-SCN-Bz-DOTA-14C5 (35.84 +/- 8.64 percentage of injected dose per g [%ID/g]) being 3.9- and 2.2-folds higher than (131)I-14C5 (12.16 +/- 1.03%ID/g) and (111)In-p-SCN-Bz-DTPA-14C5 (14.30 +/- 3.76%ID/g), respectively. Planar gamma imaging with mAb 14C5 indicated clear localization of the pancreatic tumors versus minimal normal tissue uptake. mAb 14C5 is a promising new antibody for targeting the integrin alpha(v)beta(5) for the diagnosis of and potential therapy for pancreatic cancer.
DOI: 10.1089/cbr.2009.0696
PubMed: 20423233
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In this study, the integrin alpha(v)beta(5) is studied as a target for the diagnosis of and potential therapy for human pancreatic cancer by using the radiolabeled murine monoclonal antibody (mAb) 14C5. Biopsy specimens from human pancreatic tumors were examined for the expression of the integrin alpha(v)beta(5). The pancreatic tumor cell line Capan-1 was used to test the in vitro targeting potency of mAb 14C5 labeled with 125/131-iodine and 111-indium. Internalization, retention, and metabolism were investigated in cellular radioimmunoassays. Biodistribution and tumor-targeting characteristics were studied in Capan-1 xenografts. All tumor sections were positive for the integrin alpha(v)beta(5), with an extensive positive staining of the stroma. Saturation binding experiments showed high affinity with comparable K(d)s. In vitro internalization experiments showed a longer intracellular retention of (111)In-p-benzyl isothiocyanate-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA)-14C5 in comparison to (125)I-14C5 and (111)In-p-isothiocyanatobenzyl diethylenetriaminepentaacetic acid (p-SCN-Bz-DTPA)-14C5. In vivo radioisotope tumor uptake was maximum at 48-72 hours, with the uptake of (111)In-p-SCN-Bz-DOTA-14C5 (35.84 +/- 8.64 percentage of injected dose per g [%ID/g]) being 3.9- and 2.2-folds higher than (131)I-14C5 (12.16 +/- 1.03%ID/g) and (111)In-p-SCN-Bz-DTPA-14C5 (14.30 +/- 3.76%ID/g), respectively. Planar gamma imaging with mAb 14C5 indicated clear localization of the pancreatic tumors versus minimal normal tissue uptake. mAb 14C5 is a promising new antibody for targeting the integrin alpha(v)beta(5) for the diagnosis of and potential therapy for pancreatic cancer.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">20423233</PMID><DateCreated><Year>2010</Year><Month>04</Month><Day>28</Day></DateCreated><DateCompleted><Year>2010</Year><Month>08</Month><Day>10</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1557-8852</ISSN><JournalIssue CitedMedium="Internet"><Volume>25</Volume><Issue>2</Issue><PubDate><Year>2010</Year><Month>Apr</Month></PubDate></JournalIssue><Title>Cancer biotherapy & radiopharmaceuticals</Title><ISOAbbreviation>Cancer Biother. Radiopharm.</ISOAbbreviation></Journal><ArticleTitle>Preclinical evaluation of monoclonal antibody 14C5 for targeting pancreatic cancer.</ArticleTitle><Pagination><MedlinePgn>193-205</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1089/cbr.2009.0696</ELocationID><Abstract><AbstractText>The use of radiolabeled antibodies that are able to target primary tumors as well as metastatic tumor sites with minimal reactivity to normal tissues is a promising approach for treating pancreatic cancer. In this study, the integrin alpha(v)beta(5) is studied as a target for the diagnosis of and potential therapy for human pancreatic cancer by using the radiolabeled murine monoclonal antibody (mAb) 14C5. Biopsy specimens from human pancreatic tumors were examined for the expression of the integrin alpha(v)beta(5). The pancreatic tumor cell line Capan-1 was used to test the in vitro targeting potency of mAb 14C5 labeled with 125/131-iodine and 111-indium. Internalization, retention, and metabolism were investigated in cellular radioimmunoassays. Biodistribution and tumor-targeting characteristics were studied in Capan-1 xenografts. All tumor sections were positive for the integrin alpha(v)beta(5), with an extensive positive staining of the stroma. Saturation binding experiments showed high affinity with comparable K(d)s. In vitro internalization experiments showed a longer intracellular retention of (111)In-p-benzyl isothiocyanate-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA)-14C5 in comparison to (125)I-14C5 and (111)In-p-isothiocyanatobenzyl diethylenetriaminepentaacetic acid (p-SCN-Bz-DTPA)-14C5. In vivo radioisotope tumor uptake was maximum at 48-72 hours, with the uptake of (111)In-p-SCN-Bz-DOTA-14C5 (35.84 +/- 8.64 percentage of injected dose per g [%ID/g]) being 3.9- and 2.2-folds higher than (131)I-14C5 (12.16 +/- 1.03%ID/g) and (111)In-p-SCN-Bz-DTPA-14C5 (14.30 +/- 3.76%ID/g), respectively. Planar gamma imaging with mAb 14C5 indicated clear localization of the pancreatic tumors versus minimal normal tissue uptake. mAb 14C5 is a promising new antibody for targeting the integrin alpha(v)beta(5) for the diagnosis of and potential therapy for pancreatic cancer.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Vervoort</LastName><ForeName>Liesbet</ForeName><Initials>L</Initials><Affiliation>Laboratory of Radiopharmacy, University of Ghent, Ghent, Belgium. liesbet.vervoort@ugent.be</Affiliation></Author><Author ValidYN="Y"><LastName>Burvenich</LastName><ForeName>Ingrid</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>Staelens</LastName><ForeName>Steven</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Dumolyn</LastName><ForeName>Caroline</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Waegemans</LastName><ForeName>Els</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Van Steenkiste</LastName><ForeName>Magali</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Baird</LastName><ForeName>Sarah K</ForeName><Initials>SK</Initials></Author><Author ValidYN="Y"><LastName>Scott</LastName><ForeName>Andrew M</ForeName><Initials>AM</Initials></Author><Author ValidYN="Y"><LastName>De Vos</LastName><ForeName>Filip</ForeName><Initials>F</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Cancer Biother Radiopharm</MedlineTA><NlmUniqueID>9605408</NlmUniqueID><ISSNLinking>1084-9785</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>14C5 monoclonal antibody</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Antibodies, Monoclonal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Iodine Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Radiopharmaceuticals</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Receptors, Vitronectin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>integrin alphaVbeta5</NameOfSubstance></Chemical><Chemical><RegistryNumber>102650-30-6</RegistryNumber><NameOfSubstance>1-(4-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid</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">Antibodies, 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MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Pancreatic Neoplasms</DescriptorName><QualifierName MajorTopicYN="N">immunology</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName><QualifierName MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Pentetic Acid</DescriptorName><QualifierName MajorTopicYN="N">analogs & derivatives</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Radioimmunoassay</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Radiopharmaceuticals</DescriptorName><QualifierName MajorTopicYN="Y">diagnostic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Receptors, Vitronectin</DescriptorName><QualifierName MajorTopicYN="N">immunology</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Tissue Distribution</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Tumor Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y">Xenograft Model Antitumor Assays</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>4</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>4</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>8</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1089/cbr.2009.0696</ArticleId><ArticleId 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