Internalization of indium-labeled LDL through a lipid chelating anchor in human pancreatic-cancer cells as a potential radiopharmaceutical for tumor localization.
Identifieur interne : 004094 ( Main/Exploration ); précédent : 004093; suivant : 004095Internalization of indium-labeled LDL through a lipid chelating anchor in human pancreatic-cancer cells as a potential radiopharmaceutical for tumor localization.
Auteurs : RBID : pubmed:9033634English descriptors
- KwdEn :
- Carbocyanines (pharmacokinetics), Fluorescent Dyes (pharmacokinetics), Humans, Indium Radioisotopes (diagnostic use), Indium Radioisotopes (pharmacokinetics), Lipoproteins, LDL (diagnostic use), Lipoproteins, LDL (pharmacokinetics), Pancreatic Neoplasms (metabolism), Pancreatic Neoplasms (radionuclide imaging), Radiopharmaceuticals (diagnostic use), Radiopharmaceuticals (pharmacokinetics), Tumor Cells, Cultured (metabolism).
- MESH :
- chemical , diagnostic use : Indium Radioisotopes, Lipoproteins, LDL, Radiopharmaceuticals.
- chemical , pharmacokinetics : Carbocyanines, Fluorescent Dyes, Indium Radioisotopes, Lipoproteins, LDL, Radiopharmaceuticals.
- metabolism : Pancreatic Neoplasms, Tumor Cells, Cultured.
- radionuclide imaging : Pancreatic Neoplasms.
- Humans.
Abstract
Low-density lipoproteins (LDL) labeled with indium via a lipid-chelating agent, the bis(stearylamide) of diethylenetri-aminepentaacetic acid (L), were evaluated as a potential radiopharmaceutical (111In-L-LDL) for tumor localization by studying their internalization in human pancreatic cancer cells (Capan-1). Using Dil-LDL (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate-LDL), this cell line was shown to bind human LDL with a high-affinity saturable component and a low-affinity non-saturable (40%) component. The single saturable high-affinity binding site had a KD of 27.5 +/- 2.1 micrograms/ml and a maximal binding of 610 +/- 7.5 ng/ml protein. Electron-microscopic examination of the In-L-LDL particles revealed the peripheral distribution of the electron-dense indium atoms at the outer surface of LDL. The modified LDL were then shown to be internalized by the cells. After conjugation of In-L-LDL to colloidal gold to follow the different stages of internalization, electron-microscopic examination showed that the In-L-LDL gold conjugates were stuck to the external sheet of the plasma apical and microvilli membrane, into earlier and later endosomes and into multivesicular bodies, suggesting the penetration of the In-L-LDL particles into lysosomal vacuoles. The observation of In-L-LDL-gold conjugates in deep-seated cytoplasm suggests that LDL could be employed as a drug-transport vehicle for targeting cytotoxics or radionuclides close to the cell nucleus.
PubMed: 9033634
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Using Dil-LDL (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate-LDL), this cell line was shown to bind human LDL with a high-affinity saturable component and a low-affinity non-saturable (40%) component. The single saturable high-affinity binding site had a KD of 27.5 +/- 2.1 micrograms/ml and a maximal binding of 610 +/- 7.5 ng/ml protein. Electron-microscopic examination of the In-L-LDL particles revealed the peripheral distribution of the electron-dense indium atoms at the outer surface of LDL. The modified LDL were then shown to be internalized by the cells. After conjugation of In-L-LDL to colloidal gold to follow the different stages of internalization, electron-microscopic examination showed that the In-L-LDL gold conjugates were stuck to the external sheet of the plasma apical and microvilli membrane, into earlier and later endosomes and into multivesicular bodies, suggesting the penetration of the In-L-LDL particles into lysosomal vacuoles. The observation of In-L-LDL-gold conjugates in deep-seated cytoplasm suggests that LDL could be employed as a drug-transport vehicle for targeting cytotoxics or radionuclides close to the cell nucleus.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">9033634</PMID><DateCreated><Year>1997</Year><Month>03</Month><Day>06</Day></DateCreated><DateCompleted><Year>1997</Year><Month>03</Month><Day>06</Day></DateCompleted><DateRevised><Year>2007</Year><Month>07</Month><Day>24</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0020-7136</ISSN><JournalIssue CitedMedium="Print"><Volume>70</Volume><Issue>3</Issue><PubDate><Year>1997</Year><Month>Jan</Month><Day>27</Day></PubDate></JournalIssue><Title>International journal of cancer. Journal international du cancer</Title><ISOAbbreviation>Int. J. Cancer</ISOAbbreviation></Journal><ArticleTitle>Internalization of indium-labeled LDL through a lipid chelating anchor in human pancreatic-cancer cells as a potential radiopharmaceutical for tumor localization.</ArticleTitle><Pagination><MedlinePgn>315-22</MedlinePgn></Pagination><Abstract><AbstractText>Low-density lipoproteins (LDL) labeled with indium via a lipid-chelating agent, the bis(stearylamide) of diethylenetri-aminepentaacetic acid (L), were evaluated as a potential radiopharmaceutical (111In-L-LDL) for tumor localization by studying their internalization in human pancreatic cancer cells (Capan-1). Using Dil-LDL (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate-LDL), this cell line was shown to bind human LDL with a high-affinity saturable component and a low-affinity non-saturable (40%) component. The single saturable high-affinity binding site had a KD of 27.5 +/- 2.1 micrograms/ml and a maximal binding of 610 +/- 7.5 ng/ml protein. Electron-microscopic examination of the In-L-LDL particles revealed the peripheral distribution of the electron-dense indium atoms at the outer surface of LDL. The modified LDL were then shown to be internalized by the cells. After conjugation of In-L-LDL to colloidal gold to follow the different stages of internalization, electron-microscopic examination showed that the In-L-LDL gold conjugates were stuck to the external sheet of the plasma apical and microvilli membrane, into earlier and later endosomes and into multivesicular bodies, suggesting the penetration of the In-L-LDL particles into lysosomal vacuoles. The observation of In-L-LDL-gold conjugates in deep-seated cytoplasm suggests that LDL could be employed as a drug-transport vehicle for targeting cytotoxics or radionuclides close to the cell nucleus.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Urizzi</LastName><ForeName>P</ForeName><Initials>P</Initials><Affiliation>Laboratoire de Synthèse, Physico-Chimie et Radiobiologie, Université Paul Sabatier, Toulouse, France.</Affiliation></Author><Author ValidYN="Y"><LastName>Souchard</LastName><ForeName>J P</ForeName><Initials>JP</Initials></Author><Author ValidYN="Y"><LastName>Palevody</LastName><ForeName>C</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Ratovo</LastName><ForeName>G</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Hollande</LastName><ForeName>E</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Nepveu</LastName><ForeName>F</ForeName><Initials>F</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType><PublicationType>Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>UNITED STATES</Country><MedlineTA>Int J Cancer</MedlineTA><NlmUniqueID>0042124</NlmUniqueID><ISSNLinking>0020-7136</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Carbocyanines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Fluorescent Dyes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Indium Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Lipoproteins, LDL</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Radiopharmaceuticals</NameOfSubstance></Chemical><Chemical><RegistryNumber>84109-08-0</RegistryNumber><NameOfSubstance>carbocyanine dye DiIC12(3)</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Carbocyanines</DescriptorName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Fluorescent Dyes</DescriptorName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Indium Radioisotopes</DescriptorName><QualifierName MajorTopicYN="N">diagnostic use</QualifierName><QualifierName MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Lipoproteins, LDL</DescriptorName><QualifierName MajorTopicYN="N">diagnostic use</QualifierName><QualifierName MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Pancreatic Neoplasms</DescriptorName><QualifierName MajorTopicYN="Y">metabolism</QualifierName><QualifierName MajorTopicYN="N">radionuclide imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Radiopharmaceuticals</DescriptorName><QualifierName MajorTopicYN="N">diagnostic use</QualifierName><QualifierName MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Tumor Cells, Cultured</DescriptorName><QualifierName MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1997</Year><Month>1</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2000</Year><Month>6</Month><Day>20</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1997</Year><Month>1</Month><Day>27</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">9033634</ArticleId><ArticleId IdType="pii">10.1002/(SICI)1097-0215(19970127)70:3<315::AID-IJC12>3.0.CO;2-E</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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