Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein.
Identifieur interne : 003155 ( PubMed/Corpus ); précédent : 003154; suivant : 003156Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein.
Auteurs : F. Mattner ; M. Quinlivan ; I. Greguric ; T. Pham ; X. Liu ; T. Jackson ; P. Berghofer ; C J R. Fookes ; B. Dikic ; M-C Gregoire ; F. Dolle ; A. KatsifisSource :
- Disease markers [ 1875-8630 ] ; 2015.
English descriptors
- KwdEn :
- Acetamides (chemical synthesis), Acetamides (pharmacokinetics), Animals, Brain (diagnostic imaging), Carrier Proteins (metabolism), Male, Protein Binding, Pyridines (chemical synthesis), Pyridines (pharmacokinetics), Radiopharmaceuticals (adverse effects), Radiopharmaceuticals (chemical synthesis), Radiopharmaceuticals (pharmacokinetics), Rats, Rats, Sprague-Dawley, Receptors, GABA-A (metabolism), Tissue Distribution, Tomography, Emission-Computed, Single-Photon.
- MESH :
- chemical , adverse effects : Radiopharmaceuticals.
- chemical , chemical synthesis : Acetamides, Pyridines, Radiopharmaceuticals.
- chemical , metabolism : Carrier Proteins, Receptors, GABA-A.
- chemical , pharmacokinetics : Acetamides, Pyridines, Radiopharmaceuticals.
- diagnostic imaging : Brain.
- Animals, Male, Protein Binding, Rats, Rats, Sprague-Dawley, Tissue Distribution, Tomography, Emission-Computed, Single-Photon.
Abstract
The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [(123)I]-CLINME was prepared in 70-80% radiochemical yield. The uptake of [(123)I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [(123)I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [(123)I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [(123)I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion:nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [(123)I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT.
DOI: 10.1155/2015/729698
PubMed: 26199457
Links to Exploration step
pubmed:26199457Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein.</title><author><name sortKey="Mattner, F" sort="Mattner, F" uniqKey="Mattner F" first="F" last="Mattner">F. Mattner</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia ; Department of Molecular Imaging, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Quinlivan, M" sort="Quinlivan, M" uniqKey="Quinlivan M" first="M" last="Quinlivan">M. Quinlivan</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Greguric, I" sort="Greguric, I" uniqKey="Greguric I" first="I" last="Greguric">I. Greguric</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Pham, T" sort="Pham, T" uniqKey="Pham T" first="T" last="Pham">T. Pham</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, X" sort="Liu, X" uniqKey="Liu X" first="X" last="Liu">X. 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Katsifis</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia ; Department of Molecular Imaging, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26199457</idno><idno type="pmid">26199457</idno><idno type="doi">10.1155/2015/729698</idno><idno type="wicri:Area/PubMed/Corpus">003155</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003155</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein.</title><author><name sortKey="Mattner, F" sort="Mattner, F" uniqKey="Mattner F" first="F" last="Mattner">F. Mattner</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia ; Department of Molecular Imaging, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Quinlivan, M" sort="Quinlivan, M" uniqKey="Quinlivan M" first="M" last="Quinlivan">M. Quinlivan</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Greguric, I" sort="Greguric, I" uniqKey="Greguric I" first="I" last="Greguric">I. Greguric</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Pham, T" sort="Pham, T" uniqKey="Pham T" first="T" last="Pham">T. Pham</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, X" sort="Liu, X" uniqKey="Liu X" first="X" last="Liu">X. Liu</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Jackson, T" sort="Jackson, T" uniqKey="Jackson T" first="T" last="Jackson">T. Jackson</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Berghofer, P" sort="Berghofer, P" uniqKey="Berghofer P" first="P" last="Berghofer">P. Berghofer</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Fookes, C J R" sort="Fookes, C J R" uniqKey="Fookes C" first="C J R" last="Fookes">C J R. Fookes</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Dikic, B" sort="Dikic, B" uniqKey="Dikic B" first="B" last="Dikic">B. Dikic</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Gregoire, M C" sort="Gregoire, M C" uniqKey="Gregoire M" first="M-C" last="Gregoire">M-C Gregoire</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Dolle, F" sort="Dolle, F" uniqKey="Dolle F" first="F" last="Dolle">F. Dolle</name><affiliation><nlm:affiliation>CEA, DSV/I2BM, Service Hospitalier Frédéric Joliot, 4 Place du Général Leclerc, 91401 Orsay, France.</nlm:affiliation></affiliation></author><author><name sortKey="Katsifis, A" sort="Katsifis, A" uniqKey="Katsifis A" first="A" last="Katsifis">A. Katsifis</name><affiliation><nlm:affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia ; Department of Molecular Imaging, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Disease markers</title><idno type="eISSN">1875-8630</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetamides (chemical synthesis)</term><term>Acetamides (pharmacokinetics)</term><term>Animals</term><term>Brain (diagnostic imaging)</term><term>Carrier Proteins (metabolism)</term><term>Male</term><term>Protein Binding</term><term>Pyridines (chemical synthesis)</term><term>Pyridines (pharmacokinetics)</term><term>Radiopharmaceuticals (adverse effects)</term><term>Radiopharmaceuticals (chemical synthesis)</term><term>Radiopharmaceuticals (pharmacokinetics)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Receptors, GABA-A (metabolism)</term><term>Tissue Distribution</term><term>Tomography, Emission-Computed, Single-Photon</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Radiopharmaceuticals</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Acetamides</term><term>Pyridines</term><term>Radiopharmaceuticals</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Carrier Proteins</term><term>Receptors, GABA-A</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Acetamides</term><term>Pyridines</term><term>Radiopharmaceuticals</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Male</term><term>Protein Binding</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Tissue Distribution</term><term>Tomography, Emission-Computed, Single-Photon</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [(123)I]-CLINME was prepared in 70-80% radiochemical yield. The uptake of [(123)I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [(123)I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [(123)I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [(123)I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion:nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [(123)I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26199457</PMID><DateCreated><Year>2015</Year><Month>07</Month><Day>22</Day></DateCreated><DateCompleted><Year>2016</Year><Month>04</Month><Day>26</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1875-8630</ISSN><JournalIssue CitedMedium="Internet"><Volume>2015</Volume><PubDate><Year>2015</Year></PubDate></JournalIssue><Title>Disease markers</Title><ISOAbbreviation>Dis. Markers</ISOAbbreviation></Journal><ArticleTitle>Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein.</ArticleTitle><Pagination><MedlinePgn>729698</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1155/2015/729698</ELocationID><Abstract><AbstractText>The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [(123)I]-CLINME was prepared in 70-80% radiochemical yield. The uptake of [(123)I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [(123)I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [(123)I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [(123)I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion:nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [(123)I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mattner</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia ; Department of Molecular Imaging, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Quinlivan</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Greguric</LastName><ForeName>I</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pham</LastName><ForeName>T</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>X</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jackson</LastName><ForeName>T</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Berghofer</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fookes</LastName><ForeName>C J R</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dikic</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gregoire</LastName><ForeName>M-C</ForeName><Initials>MC</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dolle</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>CEA, DSV/I2BM, Service Hospitalier Frédéric Joliot, 4 Place du Général Leclerc, 91401 Orsay, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Katsifis</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia ; Department of Molecular Imaging, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>06</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Dis Markers</MedlineTA><NlmUniqueID>8604127</NlmUniqueID><ISSNLinking>0278-0240</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C525077">2-(6-chloro-2-(4-iodophenyl)-imidazo(1,2-alpha)pyridin-3-yl)-N-ethyl-N-methyl-acetamide</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000081">Acetamides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002352">Carrier Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011725">Pyridines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019275">Radiopharmaceuticals</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011963">Receptors, GABA-A</NameOfSubstance></Chemical><Chemical><RegistryNumber>141440-82-6</RegistryNumber><NameOfSubstance UI="C069997">Tspo protein, rat</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Glia. 2002 Nov;40(2):206-17</RefSource><PMID Version="1">12379908</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Life Sci. 2006 Jun 13;79(3):287-94</RefSource><PMID 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