Uptake of indium-111 in the liver of mice following administration of indium-111-DTPA-labeled monoclonal antibodies: influence of labeling parameters, physiologic parameters, and antibody dose.
Identifieur interne : 005473 ( Main/Exploration ); précédent : 005472; suivant : 005474Uptake of indium-111 in the liver of mice following administration of indium-111-DTPA-labeled monoclonal antibodies: influence of labeling parameters, physiologic parameters, and antibody dose.
Auteurs : RBID : pubmed:2348237English descriptors
- KwdEn :
- MESH :
- chemical , administration & dosage : Antibodies, Monoclonal, Indium Radioisotopes, Pentetic Acid.
- chemical , pharmacokinetics : Indium Radioisotopes.
- metabolism : Liver.
- Animals, Isotope Labeling, Mice, Tissue Distribution.
Abstract
Liver uptake of indium-111 (111In) in mice was investigated following administration of 111In-DTPA murine monoclonal antibodies (111In-DTPA-MAbs) labeled by the cyclic anhydride method. Biodistribution of HPLC-purified 111In-DTPA-MAb preparations was checked with a low (0.2 micrograms) and a high (8.0 micrograms) MAb dose. Using Bio Gel P-30 for desalting the MAb-conjugates, 111In uptake in the liver amounted to 8%-9% of the injected dose (ID) and was independent from the MAb dose, the DTPA-to-MAb molar ratio, tumor growth and biologic variability (different MAbs and different strains of mice). Using Sephadex G-25 for desalting, 0.2 micrograms doses from 7 out of 26 preparations showed increased liver accumulation of 111In in non-tumor mice ranging from 15%-25% of ID. Corresponding high doses led to a "normal" value of 8%-9%. Increased liver uptake of the low dose could not be reduced by coadministration of the unconjugated MAb, but was normal after reinjection of "in vivo filtered" material. An inverse intracellular distribution of 111In activity between sediment and supernatant of liver homogenates, following the administration of the low and the high MAb dose, indicated an artifact of the labeling procedure rather than an inherent biological property of labeled MAbs.
PubMed: 2348237
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Le document en format XML
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<author><name sortKey="Schuhmacher, J" uniqKey="Schuhmacher J">J Schuhmacher</name>
<affiliation wicri:level="3"><nlm:affiliation>Institute of Radiology and Pathophysiology, German Cancer Research Center, Heidelberg, FRG.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Radiology and Pathophysiology, 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="Matys, R" uniqKey="Matys R">R Matys</name>
</author>
<author><name sortKey="Kirchgebner, H" uniqKey="Kirchgebner H">H Kirchgebner</name>
</author>
<author><name sortKey="Hauser, H" uniqKey="Hauser H">H Hauser</name>
</author>
<author><name sortKey="Maier Borst, W" uniqKey="Maier Borst W">W Maier-Borst</name>
</author>
<author><name sortKey="Matzku, S" uniqKey="Matzku S">S Matzku</name>
</author>
</titleStmt>
<publicationStmt><date when="1990">1990</date>
<idno type="RBID">pubmed:2348237</idno>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antibodies, Monoclonal (administration & dosage)</term>
<term>Indium Radioisotopes (administration & dosage)</term>
<term>Indium Radioisotopes (pharmacokinetics)</term>
<term>Isotope Labeling</term>
<term>Liver (metabolism)</term>
<term>Mice</term>
<term>Pentetic Acid (administration & dosage)</term>
<term>Tissue Distribution</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Indium Radioisotopes</term>
<term>Pentetic Acid</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Indium Radioisotopes</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Liver</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Isotope Labeling</term>
<term>Mice</term>
<term>Tissue Distribution</term>
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<front><div type="abstract" xml:lang="en">Liver uptake of indium-111 (111In) in mice was investigated following administration of 111In-DTPA murine monoclonal antibodies (111In-DTPA-MAbs) labeled by the cyclic anhydride method. Biodistribution of HPLC-purified 111In-DTPA-MAb preparations was checked with a low (0.2 micrograms) and a high (8.0 micrograms) MAb dose. Using Bio Gel P-30 for desalting the MAb-conjugates, 111In uptake in the liver amounted to 8%-9% of the injected dose (ID) and was independent from the MAb dose, the DTPA-to-MAb molar ratio, tumor growth and biologic variability (different MAbs and different strains of mice). Using Sephadex G-25 for desalting, 0.2 micrograms doses from 7 out of 26 preparations showed increased liver accumulation of 111In in non-tumor mice ranging from 15%-25% of ID. Corresponding high doses led to a "normal" value of 8%-9%. Increased liver uptake of the low dose could not be reduced by coadministration of the unconjugated MAb, but was normal after reinjection of "in vivo filtered" material. An inverse intracellular distribution of 111In activity between sediment and supernatant of liver homogenates, following the administration of the low and the high MAb dose, indicated an artifact of the labeling procedure rather than an inherent biological property of labeled MAbs.</div>
</front>
</TEI>
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<DateCreated><Year>1990</Year>
<Month>07</Month>
<Day>12</Day>
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<DateCompleted><Year>1990</Year>
<Month>07</Month>
<Day>12</Day>
</DateCompleted>
<DateRevised><Year>2013</Year>
<Month>11</Month>
<Day>21</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Print">0161-5505</ISSN>
<JournalIssue CitedMedium="Print"><Volume>31</Volume>
<Issue>6</Issue>
<PubDate><Year>1990</Year>
<Month>Jun</Month>
</PubDate>
</JournalIssue>
<Title>Journal of nuclear medicine : official publication, Society of Nuclear Medicine</Title>
<ISOAbbreviation>J. Nucl. Med.</ISOAbbreviation>
</Journal>
<ArticleTitle>Uptake of indium-111 in the liver of mice following administration of indium-111-DTPA-labeled monoclonal antibodies: influence of labeling parameters, physiologic parameters, and antibody dose.</ArticleTitle>
<Pagination><MedlinePgn>1084-93</MedlinePgn>
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<Abstract><AbstractText>Liver uptake of indium-111 (111In) in mice was investigated following administration of 111In-DTPA murine monoclonal antibodies (111In-DTPA-MAbs) labeled by the cyclic anhydride method. Biodistribution of HPLC-purified 111In-DTPA-MAb preparations was checked with a low (0.2 micrograms) and a high (8.0 micrograms) MAb dose. Using Bio Gel P-30 for desalting the MAb-conjugates, 111In uptake in the liver amounted to 8%-9% of the injected dose (ID) and was independent from the MAb dose, the DTPA-to-MAb molar ratio, tumor growth and biologic variability (different MAbs and different strains of mice). Using Sephadex G-25 for desalting, 0.2 micrograms doses from 7 out of 26 preparations showed increased liver accumulation of 111In in non-tumor mice ranging from 15%-25% of ID. Corresponding high doses led to a "normal" value of 8%-9%. Increased liver uptake of the low dose could not be reduced by coadministration of the unconjugated MAb, but was normal after reinjection of "in vivo filtered" material. An inverse intracellular distribution of 111In activity between sediment and supernatant of liver homogenates, following the administration of the low and the high MAb dose, indicated an artifact of the labeling procedure rather than an inherent biological property of labeled MAbs.</AbstractText>
</Abstract>
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<MedlineJournalInfo><Country>UNITED STATES</Country>
<MedlineTA>J Nucl Med</MedlineTA>
<NlmUniqueID>0217410</NlmUniqueID>
<ISSNLinking>0161-5505</ISSNLinking>
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<NameOfSubstance>Antibodies, Monoclonal</NameOfSubstance>
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<NameOfSubstance>Indium Radioisotopes</NameOfSubstance>
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<Chemical><RegistryNumber>7A314HQM0I</RegistryNumber>
<NameOfSubstance>Pentetic Acid</NameOfSubstance>
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<MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Animals</DescriptorName>
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<MeshHeading><DescriptorName MajorTopicYN="N">Antibodies, Monoclonal</DescriptorName>
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<MeshHeading><DescriptorName MajorTopicYN="N">Indium Radioisotopes</DescriptorName>
<QualifierName MajorTopicYN="N">administration & dosage</QualifierName>
<QualifierName MajorTopicYN="Y">pharmacokinetics</QualifierName>
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<MeshHeading><DescriptorName MajorTopicYN="N">Isotope Labeling</DescriptorName>
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<MeshHeading><DescriptorName MajorTopicYN="N">Liver</DescriptorName>
<QualifierName MajorTopicYN="Y">metabolism</QualifierName>
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<MeshHeading><DescriptorName MajorTopicYN="N">Mice</DescriptorName>
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<MeshHeading><DescriptorName MajorTopicYN="N">Pentetic Acid</DescriptorName>
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<MeshHeading><DescriptorName MajorTopicYN="N">Tissue Distribution</DescriptorName>
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