Novel neurotensin analogues for radioisotope targeting to neurotensin receptor-positive tumors.
Identifieur interne : 001D47 ( Main/Exploration ); précédent : 001D46; suivant : 001D48Novel neurotensin analogues for radioisotope targeting to neurotensin receptor-positive tumors.
Auteurs : RBID : pubmed:19610615English descriptors
- KwdEn :
- Adenocarcinoma (diagnosis), Adenocarcinoma (metabolism), Animals, Breast Neoplasms (diagnosis), Breast Neoplasms (metabolism), Cell Line, Tumor, Female, Humans, Indium Radioisotopes (metabolism), Indium Radioisotopes (pharmacokinetics), Ligands, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasms (diagnosis), Neoplasms (metabolism), Neurotensin (analogs & derivatives), Neurotensin (metabolism), Neurotensin (pharmacokinetics), Pancreatic Neoplasms (diagnosis), Pancreatic Neoplasms (metabolism), Pentetic Acid (metabolism), Pentetic Acid (pharmacokinetics), Receptors, Neurotensin (metabolism), Tissue Distribution.
- MESH :
- chemical , analogs & derivatives : Neurotensin.
- chemical , metabolism : Indium Radioisotopes, Neurotensin, Pentetic Acid, Receptors, Neurotensin.
- diagnosis : Adenocarcinoma, Breast Neoplasms, Neoplasms, Pancreatic Neoplasms.
- metabolism : Adenocarcinoma, Breast Neoplasms, Neoplasms, Pancreatic Neoplasms.
- chemical , pharmacokinetics : Indium Radioisotopes, Neurotensin, Pentetic Acid.
- Animals, Cell Line, Tumor, Female, Humans, Ligands, Mice, Mice, Inbred BALB C, Mice, Nude, Tissue Distribution.
Abstract
The increased expression of the neurotensin (NT) receptor NTS1 by different cancer cells, such as pancreatic adenocarcinoma and ductal breast cancer cells, as compared to normal epithelium, offers the opportunity to target these tumors with radiolabeled neurotensin analogues for diagnostic or therapeutic purposes. The aim of the present study was to design and synthesize new neurotensin radioligands and to select a lead molecule with high in vivo tumor selectivity for further development. Two series of neurotensin analogues bearing DTPA were tested: a series of NT(8-13) analogues, with DTPA coupled to the α-NH(2), sharing the same peptide sequence with analogues previously developed for radiolabeling with technetium or rhenium, as well as an NT(6-13) series in which DTPA was coupled to the ε-NH(2) of Lys(6). Changes were introduced to stabilize the bonds between Arg(8)-Arg(9), Pro(10)-Tyr(11), and Tyr(11)-Ile(12) to provide metabolic stability. Structure-activity studies of NT analogues have shown that the attachment of DTPA induces an important loss of affinity unless the distance between the chelator and the NT(8-13) sequence, which binds to the NTS1 receptor, is increased. The doubly stabilized DTPA-NT-20.3 exhibits a high affinity and an elevated stability to enzymatic degradation. It shows specific tumor uptake and high tumor to blood, to liver, and to intestine activity uptake ratios and affords high-contrast planar and SPECT images in an animal model. The DTPA-NT-20.3 peptide is a promising candidate for imaging neurotensin receptor-positive tumors, such as pancreatic adenocarcinoma and invasive ductal breast cancer. Analogues carrying DOTA are being developed for yttrium-90 or lutetium-177 labeling.
DOI: 10.1021/bc900151z
PubMed: 19610615
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Novel neurotensin analogues for radioisotope targeting to neurotensin receptor-positive tumors.</title><author><name sortKey="Alshoukr, Faisal" uniqKey="Alshoukr F">Faisal Alshoukr</name><affiliation wicri:level="1"><nlm:affiliation>Inserm, U773, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U773, Paris</wicri:regionArea><placeName><region type="région">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Rosant, Cedric" uniqKey="Rosant C">Cedric Rosant</name></author><author><name sortKey="Maes, Veronique" uniqKey="Maes V">Veronique Maes</name></author><author><name sortKey="Abdelhak, Jallane" uniqKey="Abdelhak J">Jallane Abdelhak</name></author><author><name sortKey="Raguin, Olivier" uniqKey="Raguin O">Olivier Raguin</name></author><author><name sortKey="Burg, Samuel" uniqKey="Burg S">Samuel Burg</name></author><author><name sortKey="Sarda, Laure" uniqKey="Sarda L">Laure Sarda</name></author><author><name sortKey="Barbet, Jacques" uniqKey="Barbet J">Jacques Barbet</name></author><author><name sortKey="Tourwe, Dirk" uniqKey="Tourwe D">Dirk Tourwé</name></author><author><name sortKey="Pelaprat, Didier" uniqKey="Pelaprat D">Didier Pelaprat</name></author><author><name sortKey="Gruaz Guyon, Anne" uniqKey="Gruaz Guyon A">Anne Gruaz-Guyon</name></author></titleStmt><publicationStmt><date when="2009">2009</date><idno type="doi">10.1021/bc900151z</idno><idno type="RBID">pubmed:19610615</idno><idno type="pmid">19610615</idno><idno type="wicri:Area/Main/Corpus">001D76</idno><idno type="wicri:Area/Main/Curation">001D76</idno><idno type="wicri:Area/Main/Exploration">001D47</idno></publicationStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenocarcinoma (diagnosis)</term><term>Adenocarcinoma (metabolism)</term><term>Animals</term><term>Breast Neoplasms (diagnosis)</term><term>Breast Neoplasms (metabolism)</term><term>Cell Line, Tumor</term><term>Female</term><term>Humans</term><term>Indium Radioisotopes (metabolism)</term><term>Indium Radioisotopes (pharmacokinetics)</term><term>Ligands</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Nude</term><term>Neoplasms (diagnosis)</term><term>Neoplasms (metabolism)</term><term>Neurotensin (analogs & derivatives)</term><term>Neurotensin (metabolism)</term><term>Neurotensin (pharmacokinetics)</term><term>Pancreatic Neoplasms (diagnosis)</term><term>Pancreatic Neoplasms (metabolism)</term><term>Pentetic Acid (metabolism)</term><term>Pentetic Acid (pharmacokinetics)</term><term>Receptors, Neurotensin (metabolism)</term><term>Tissue Distribution</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Neurotensin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Indium Radioisotopes</term><term>Neurotensin</term><term>Pentetic Acid</term><term>Receptors, Neurotensin</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Adenocarcinoma</term><term>Breast Neoplasms</term><term>Neoplasms</term><term>Pancreatic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Adenocarcinoma</term><term>Breast Neoplasms</term><term>Neoplasms</term><term>Pancreatic Neoplasms</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Indium Radioisotopes</term><term>Neurotensin</term><term>Pentetic Acid</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Female</term><term>Humans</term><term>Ligands</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Nude</term><term>Tissue Distribution</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The increased expression of the neurotensin (NT) receptor NTS1 by different cancer cells, such as pancreatic adenocarcinoma and ductal breast cancer cells, as compared to normal epithelium, offers the opportunity to target these tumors with radiolabeled neurotensin analogues for diagnostic or therapeutic purposes. The aim of the present study was to design and synthesize new neurotensin radioligands and to select a lead molecule with high in vivo tumor selectivity for further development. Two series of neurotensin analogues bearing DTPA were tested: a series of NT(8-13) analogues, with DTPA coupled to the α-NH(2), sharing the same peptide sequence with analogues previously developed for radiolabeling with technetium or rhenium, as well as an NT(6-13) series in which DTPA was coupled to the ε-NH(2) of Lys(6). Changes were introduced to stabilize the bonds between Arg(8)-Arg(9), Pro(10)-Tyr(11), and Tyr(11)-Ile(12) to provide metabolic stability. Structure-activity studies of NT analogues have shown that the attachment of DTPA induces an important loss of affinity unless the distance between the chelator and the NT(8-13) sequence, which binds to the NTS1 receptor, is increased. The doubly stabilized DTPA-NT-20.3 exhibits a high affinity and an elevated stability to enzymatic degradation. It shows specific tumor uptake and high tumor to blood, to liver, and to intestine activity uptake ratios and affords high-contrast planar and SPECT images in an animal model. The DTPA-NT-20.3 peptide is a promising candidate for imaging neurotensin receptor-positive tumors, such as pancreatic adenocarcinoma and invasive ductal breast cancer. Analogues carrying DOTA are being developed for yttrium-90 or lutetium-177 labeling.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">19610615</PMID><DateCreated><Year>2010</Year><Month>12</Month><Day>14</Day></DateCreated><DateCompleted><Year>2011</Year><Month>04</Month><Day>04</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1520-4812</ISSN><JournalIssue CitedMedium="Internet"><Volume>20</Volume><Issue>8</Issue><PubDate><Year>2009</Year><Month>Aug</Month><Day>19</Day></PubDate></JournalIssue><Title>Bioconjugate chemistry</Title><ISOAbbreviation>Bioconjug. Chem.</ISOAbbreviation></Journal><ArticleTitle>Novel neurotensin analogues for radioisotope targeting to neurotensin receptor-positive tumors.</ArticleTitle><Pagination><MedlinePgn>1602-10</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/bc900151z</ELocationID><Abstract><AbstractText>The increased expression of the neurotensin (NT) receptor NTS1 by different cancer cells, such as pancreatic adenocarcinoma and ductal breast cancer cells, as compared to normal epithelium, offers the opportunity to target these tumors with radiolabeled neurotensin analogues for diagnostic or therapeutic purposes. The aim of the present study was to design and synthesize new neurotensin radioligands and to select a lead molecule with high in vivo tumor selectivity for further development. Two series of neurotensin analogues bearing DTPA were tested: a series of NT(8-13) analogues, with DTPA coupled to the α-NH(2), sharing the same peptide sequence with analogues previously developed for radiolabeling with technetium or rhenium, as well as an NT(6-13) series in which DTPA was coupled to the ε-NH(2) of Lys(6). Changes were introduced to stabilize the bonds between Arg(8)-Arg(9), Pro(10)-Tyr(11), and Tyr(11)-Ile(12) to provide metabolic stability. Structure-activity studies of NT analogues have shown that the attachment of DTPA induces an important loss of affinity unless the distance between the chelator and the NT(8-13) sequence, which binds to the NTS1 receptor, is increased. The doubly stabilized DTPA-NT-20.3 exhibits a high affinity and an elevated stability to enzymatic degradation. It shows specific tumor uptake and high tumor to blood, to liver, and to intestine activity uptake ratios and affords high-contrast planar and SPECT images in an animal model. The DTPA-NT-20.3 peptide is a promising candidate for imaging neurotensin receptor-positive tumors, such as pancreatic adenocarcinoma and invasive ductal breast cancer. Analogues carrying DOTA are being developed for yttrium-90 or lutetium-177 labeling.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alshoukr</LastName><ForeName>Faisal</ForeName><Initials>F</Initials><Affiliation>Inserm, U773, Paris, France.</Affiliation></Author><Author ValidYN="Y"><LastName>Rosant</LastName><ForeName>Cedric</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Maes</LastName><ForeName>Veronique</ForeName><Initials>V</Initials></Author><Author ValidYN="Y"><LastName>Abdelhak</LastName><ForeName>Jallane</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Raguin</LastName><ForeName>Olivier</ForeName><Initials>O</Initials></Author><Author ValidYN="Y"><LastName>Burg</LastName><ForeName>Samuel</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Sarda</LastName><ForeName>Laure</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Barbet</LastName><ForeName>Jacques</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Tourwé</LastName><ForeName>Dirk</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Pelaprat</LastName><ForeName>Didier</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Gruaz-Guyon</LastName><ForeName>Anne</ForeName><Initials>A</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType><PublicationType>Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>07</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Bioconjug Chem</MedlineTA><NlmUniqueID>9010319</NlmUniqueID><ISSNLinking>1043-1802</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Indium Radioisotopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Ligands</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Receptors, Neurotensin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>neurotensin type 1 receptor</NameOfSubstance></Chemical><Chemical><RegistryNumber>39379-15-2</RegistryNumber><NameOfSubstance>Neurotensin</NameOfSubstance></Chemical><Chemical><RegistryNumber>7A314HQM0I</RegistryNumber><NameOfSubstance>Pentetic Acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Adenocarcinoma</DescriptorName><QualifierName MajorTopicYN="N">diagnosis</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Breast Neoplasms</DescriptorName><QualifierName MajorTopicYN="N">diagnosis</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Indium Radioisotopes</DescriptorName><QualifierName MajorTopicYN="N">metabolism</QualifierName><QualifierName MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Ligands</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice, Nude</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Neoplasms</DescriptorName><QualifierName MajorTopicYN="N">diagnosis</QualifierName><QualifierName MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Neurotensin</DescriptorName><QualifierName MajorTopicYN="Y">analogs & derivatives</QualifierName><QualifierName MajorTopicYN="Y">metabolism</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Pancreatic Neoplasms</DescriptorName><QualifierName MajorTopicYN="N">diagnosis</QualifierName><QualifierName MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Pentetic Acid</DescriptorName><QualifierName MajorTopicYN="Y">metabolism</QualifierName><QualifierName MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Receptors, Neurotensin</DescriptorName><QualifierName MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Tissue Distribution</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="aheadofprint"><Year>2009</Year><Month>7</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2009</Year><Month>7</Month><Day>21</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2009</Year><Month>7</Month><Day>21</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2011</Year><Month>4</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1021/bc900151z</ArticleId><ArticleId IdType="pubmed">19610615</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix 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