Introduction of Peripheral Carboxylates to Decrease the Charge on Tm(3+) DOTAM-Alkyl Complexes: Implications for Detection Sensitivity and in Vivo Toxicity of PARACEST MRI Contrast Agents.
Identifieur interne : 000058 ( PubMed/Corpus ); précédent : 000057; suivant : 000059Introduction of Peripheral Carboxylates to Decrease the Charge on Tm(3+) DOTAM-Alkyl Complexes: Implications for Detection Sensitivity and in Vivo Toxicity of PARACEST MRI Contrast Agents.
Auteurs : Mojmír Such ; Mark Milne ; Adam A H. Elmehriki ; Nevin Mcvicar ; Alex X. Li ; Robert Bartha ; Robert H E. HudsonSource :
- Journal of medicinal chemistry [ 1520-4804 ] ; 2015.
English descriptors
- KwdEn :
- Animals, Aspartic Acid (chemistry), Carboxylic Acids (chemistry), Carboxylic Acids (pharmacology), Contrast Media (chemical synthesis), Contrast Media (toxicity), Electron Spin Resonance Spectroscopy, Kidney (anatomy & histology), Magnetic Resonance Imaging, Mice, Mice, Inbred C57BL, Organometallic Compounds (chemical synthesis), Organometallic Compounds (toxicity), Thulium (chemistry).
- MESH :
- chemical , chemical synthesis : Contrast Media, Organometallic Compounds.
- chemical , chemistry : Aspartic Acid, Carboxylic Acids, Thulium.
- chemical , pharmacology : Carboxylic Acids.
- chemical , toxicity : Contrast Media, Organometallic Compounds.
- anatomy & histology : Kidney.
- Animals, Electron Spin Resonance Spectroscopy, Magnetic Resonance Imaging, Mice, Mice, Inbred C57BL.
Abstract
A series of structurally modified Tm(3+) DOTAM-alkyl complexes as potential PARACEST MRI contrast agents has been synthesized with the aim to decrease the overall positive charge associated with these molecules and increase their biocompatibility. Two types of structural modification have been performed, an introduction of terminal carboxylate arms to the alkyl side chains and a conjugation of one of the alkyl side chains with aspartic acid. Detailed evaluation of the magnetic resonance imaging chemical exchange contrast associated with the structurally modified contrast agents has been performed. In contrast to the acutely toxic Tm(3+) DOTAM-alkyl complexes, the structurally modified compounds were found to be tolerated well during in vivo MRI studies in mice; however, only the aspartic acid modified chelates produced an amide proton-based PARACEST signal.
DOI: 10.1021/acs.jmedchem.5b00621
PubMed: 26214576
Links to Exploration step
pubmed:26214576Le document en format XML
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Elmehriki</name><affiliation><nlm:affiliation>Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Mcvicar, Nevin" sort="Mcvicar, Nevin" uniqKey="Mcvicar N" first="Nevin" last="Mcvicar">Nevin Mcvicar</name><affiliation><nlm:affiliation>Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Alex X" sort="Li, Alex X" uniqKey="Li A" first="Alex X" last="Li">Alex X. Li</name><affiliation><nlm:affiliation>Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Bartha, Robert" sort="Bartha, Robert" uniqKey="Bartha R" first="Robert" last="Bartha">Robert Bartha</name><affiliation><nlm:affiliation>Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Hudson, Robert H E" sort="Hudson, Robert H E" uniqKey="Hudson R" first="Robert H E" last="Hudson">Robert H E. Hudson</name><affiliation><nlm:affiliation>Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="doi">10.1021/acs.jmedchem.5b00621</idno><idno type="RBID">pubmed:26214576</idno><idno type="pmid">26214576</idno><idno type="wicri:Area/PubMed/Corpus">000058</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000058</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Introduction of Peripheral Carboxylates to Decrease the Charge on Tm(3+) DOTAM-Alkyl Complexes: Implications for Detection Sensitivity and in Vivo Toxicity of PARACEST MRI Contrast Agents.</title><author><name sortKey="Such, Mojmir" sort="Such, Mojmir" uniqKey="Such M" first="Mojmír" last="Such">Mojmír Such</name><affiliation><nlm:affiliation>Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Milne, Mark" sort="Milne, Mark" uniqKey="Milne M" first="Mark" last="Milne">Mark Milne</name><affiliation><nlm:affiliation>Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Elmehriki, Adam A H" sort="Elmehriki, Adam A H" uniqKey="Elmehriki A" first="Adam A H" last="Elmehriki">Adam A H. Elmehriki</name><affiliation><nlm:affiliation>Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Mcvicar, Nevin" sort="Mcvicar, Nevin" uniqKey="Mcvicar N" first="Nevin" last="Mcvicar">Nevin Mcvicar</name><affiliation><nlm:affiliation>Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Alex X" sort="Li, Alex X" uniqKey="Li A" first="Alex X" last="Li">Alex X. Li</name><affiliation><nlm:affiliation>Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Bartha, Robert" sort="Bartha, Robert" uniqKey="Bartha R" first="Robert" last="Bartha">Robert Bartha</name><affiliation><nlm:affiliation>Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Hudson, Robert H E" sort="Hudson, Robert H E" uniqKey="Hudson R" first="Robert H E" last="Hudson">Robert H E. Hudson</name><affiliation><nlm:affiliation>Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of medicinal chemistry</title><idno type="eISSN">1520-4804</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Aspartic Acid (chemistry)</term><term>Carboxylic Acids (chemistry)</term><term>Carboxylic Acids (pharmacology)</term><term>Contrast Media (chemical synthesis)</term><term>Contrast Media (toxicity)</term><term>Electron Spin Resonance Spectroscopy</term><term>Kidney (anatomy & histology)</term><term>Magnetic Resonance Imaging</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Organometallic Compounds (chemical synthesis)</term><term>Organometallic Compounds (toxicity)</term><term>Thulium (chemistry)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Contrast Media</term><term>Organometallic Compounds</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Aspartic Acid</term><term>Carboxylic Acids</term><term>Thulium</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Carboxylic Acids</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Contrast Media</term><term>Organometallic Compounds</term></keywords><keywords scheme="MESH" qualifier="anatomy & histology" xml:lang="en"><term>Kidney</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Electron Spin Resonance Spectroscopy</term><term>Magnetic Resonance Imaging</term><term>Mice</term><term>Mice, Inbred C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A series of structurally modified Tm(3+) DOTAM-alkyl complexes as potential PARACEST MRI contrast agents has been synthesized with the aim to decrease the overall positive charge associated with these molecules and increase their biocompatibility. Two types of structural modification have been performed, an introduction of terminal carboxylate arms to the alkyl side chains and a conjugation of one of the alkyl side chains with aspartic acid. Detailed evaluation of the magnetic resonance imaging chemical exchange contrast associated with the structurally modified contrast agents has been performed. In contrast to the acutely toxic Tm(3+) DOTAM-alkyl complexes, the structurally modified compounds were found to be tolerated well during in vivo MRI studies in mice; however, only the aspartic acid modified chelates produced an amide proton-based PARACEST signal.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">26214576</PMID><DateCreated><Year>2015</Year><Month>08</Month><Day>28</Day></DateCreated><DateCompleted><Year>2015</Year><Month>11</Month><Day>16</Day></DateCompleted><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1520-4804</ISSN><JournalIssue CitedMedium="Internet"><Volume>58</Volume><Issue>16</Issue><PubDate><Year>2015</Year><Month>Aug</Month><Day>27</Day></PubDate></JournalIssue><Title>Journal of medicinal chemistry</Title><ISOAbbreviation>J. Med. Chem.</ISOAbbreviation></Journal><ArticleTitle>Introduction of Peripheral Carboxylates to Decrease the Charge on Tm(3+) DOTAM-Alkyl Complexes: Implications for Detection Sensitivity and in Vivo Toxicity of PARACEST MRI Contrast Agents.</ArticleTitle><Pagination><MedlinePgn>6516-32</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/acs.jmedchem.5b00621</ELocationID><Abstract><AbstractText>A series of structurally modified Tm(3+) DOTAM-alkyl complexes as potential PARACEST MRI contrast agents has been synthesized with the aim to decrease the overall positive charge associated with these molecules and increase their biocompatibility. Two types of structural modification have been performed, an introduction of terminal carboxylate arms to the alkyl side chains and a conjugation of one of the alkyl side chains with aspartic acid. Detailed evaluation of the magnetic resonance imaging chemical exchange contrast associated with the structurally modified contrast agents has been performed. In contrast to the acutely toxic Tm(3+) DOTAM-alkyl complexes, the structurally modified compounds were found to be tolerated well during in vivo MRI studies in mice; however, only the aspartic acid modified chelates produced an amide proton-based PARACEST signal.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Suchý</LastName><ForeName>Mojmír</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Milne</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Elmehriki</LastName><ForeName>Adam A H</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McVicar</LastName><ForeName>Nevin</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Alex X</ForeName><Initials>AX</Initials><AffiliationInfo><Affiliation>Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bartha</LastName><ForeName>Robert</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Medical Biophysics, The University of Western Ontario , London, Ontario N6A 5K8, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hudson</LastName><ForeName>Robert H E</ForeName><Initials>RH</Initials><AffiliationInfo><Affiliation>Department of Chemistry, The University of Western Ontario , Chemistry Building, London, Ontario N6A 5B7, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre for Advanced Materials and Biomaterials Research, The University of Western Ontario , London, Ontario N6A 5B7, Canada.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>08</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Med Chem</MedlineTA><NlmUniqueID>9716531</NlmUniqueID><ISSNLinking>0022-2623</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C533989">(1,4,7,10-tetrakis((N-(1H-imidazol-2-yl)carbamoyl)methyl)-1,4,7,10-tetraazacyclododecane)thulium(III)</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002264">Carboxylic Acids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D003287">Contrast Media</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009942">Organometallic 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UI="Q000138">chemical synthesis</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000633">toxicity</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D004578">Electron Spin Resonance Spectroscopy</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007668">Kidney</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000033">anatomy & histology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008279">Magnetic Resonance Imaging</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D051379">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008810">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D009942">Organometallic Compounds</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000138">chemical synthesis</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000633">toxicity</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013932">Thulium</DescriptorName><QualifierName MajorTopicYN="Y" UI="Q000737">chemistry</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="aheadofprint"><Year>2015</Year><Month>8</Month><Day>6</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>7</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>7</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>11</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="doi">10.1021/acs.jmedchem.5b00621</ArticleId><ArticleId IdType="pubmed">26214576</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour 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