In vivo binding of a tau imaging probe, [11C]PBB3, in patients with progressive supranuclear palsy
Background [11C]pyridinyl‐butadienyl‐benzothiazole 3 is a PET imaging agent designed for capturing pathological tau aggregates in diverse neurodegenerative disorders, and would be of clinical utility for neuropathological investigations of PSP. Objectives To explore the usefulness of [11C]pyridinyl‐...
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| Veröffentlicht in: | Movement disorders 2019-05, Vol.34 (5), p.744-754 |
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| creator | Endo, Hironobu Shimada, Hitoshi Sahara, Naruhiko Ono, Maiko Koga, Shunsuke Kitamura, Soichiro Niwa, Fumitoshi Hirano, Shigeki Kimura, Yasuyuki Ichise, Masanori Shinotoh, Hitoshi Zhang, Ming Rong Kuwabara, Satoshi Dickson, Dennis W. Toda, Tatsushi Suhara, Tetsuya Higuchi, Makoto |
| description | Background
[11C]pyridinyl‐butadienyl‐benzothiazole 3 is a PET imaging agent designed for capturing pathological tau aggregates in diverse neurodegenerative disorders, and would be of clinical utility for neuropathological investigations of PSP.
Objectives
To explore the usefulness of [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET in assessing characteristic distributions of tau pathologies and their association with clinical symptoms in the brains of living PSP patients.
Methods
We assessed 13 PSP patients and 13 age‐matched healthy control subjects. Individuals negative for amyloid β PET with [11C]Pittsburgh compound B underwent clinical scoring, MR scans, and [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET.
Results
There were significant differences in binding potential for [11C]pyridinyl‐butadienyl‐benzothiazole 3 between PSP patients and healthy control subjects (P = 0.02). PSP patients exhibited greater radioligand retention than healthy control subjects in multiple brain regions, including frontoparietal white matter, parietal gray matter, globus pallidus, STN, red nucleus, and cerebellar dentate nucleus. [11C]pyridinyl‐butadienyl‐benzothiazole 3 deposition in frontoparietal white matter, but not gray matter, was correlated with general severity of parkinsonian and PSP symptoms, whereas both gray matter and white matter [11C]pyridinyl‐butadienyl‐benzothiazole 3 accumulations in the frontoparietal cortices were associated with nonverbal cognitive impairments. Autoradiographic and fluorescence labeling with pyridinyl‐butadienyl‐benzothiazole 3 was observed in gray matter and white matter of PSP motor cortex tissues.
Conclusions
Our findings support the in vivo detectability of tau fibrils characteristic of PSP by [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET, and imply distinct and synergistic contributions of gray matter and white matte tau pathologies to clinical symptoms. [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET potentially provides a neuroimaging‐based index for the evolution of PSP tau pathologies promoting the deterioration of motor and cognitive functions. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. |
| doi_str_mv | 10.1002/mds.27643 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6593859</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2225214733</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4873-b3a3f56c3db0b8232503290309e8dec4ed454f5c3e3250931f14712cbce752b43</originalsourceid><addsrcrecordid>eNp1kU9r3DAQxUVISbbbHvIFgiCXFuJE0lhr-RJotv8CKQm0PZUiJFneKHglV7I37Lev3E1DW-hhGJj58XgzD6EjSs4oIex83aQzVi1K2EMzyoEWgvFqH82IELwAKvghep7SPSGUcro4QIdARM0qqGdIX3m8cZuAtfON8yscWqzwoEbs1mo1DfoYtD3F3yhdfr-9vIRT7Dzu1eCsHxJ-cMPdhKyiTcltLE5jH5UfTWdVzFiXti_QszZ3-_Kxz9HX9---LD8W1zcfrpZvrgtTigoKDQpavjDQaKIFA8YJsJoAqa1orCltU_Ky5QbstKqBtrSsKDPa2IozXcIcXex0-1GvbWOyv6g62cd8SdzKoJz8e-PdnVyFjVzwGkSuOXr1KBDDj9GmQa5dMrbrlLdhTJLRuuT5cTChJ_-g92GMPp8nGWOcZWsAmXq9o0wMKUXbPpmhRE7JyZyc_JVcZo__dP9E_o4qA-c74MF1dvt_Jfnp7eed5E9sj6H2</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2225214733</pqid></control><display><type>article</type><title>In vivo binding of a tau imaging probe, [11C]PBB3, in patients with progressive supranuclear palsy</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Endo, Hironobu ; Shimada, Hitoshi ; Sahara, Naruhiko ; Ono, Maiko ; Koga, Shunsuke ; Kitamura, Soichiro ; Niwa, Fumitoshi ; Hirano, Shigeki ; Kimura, Yasuyuki ; Ichise, Masanori ; Shinotoh, Hitoshi ; Zhang, Ming Rong ; Kuwabara, Satoshi ; Dickson, Dennis W. ; Toda, Tatsushi ; Suhara, Tetsuya ; Higuchi, Makoto</creator><creatorcontrib>Endo, Hironobu ; Shimada, Hitoshi ; Sahara, Naruhiko ; Ono, Maiko ; Koga, Shunsuke ; Kitamura, Soichiro ; Niwa, Fumitoshi ; Hirano, Shigeki ; Kimura, Yasuyuki ; Ichise, Masanori ; Shinotoh, Hitoshi ; Zhang, Ming Rong ; Kuwabara, Satoshi ; Dickson, Dennis W. ; Toda, Tatsushi ; Suhara, Tetsuya ; Higuchi, Makoto</creatorcontrib><description>Background
[11C]pyridinyl‐butadienyl‐benzothiazole 3 is a PET imaging agent designed for capturing pathological tau aggregates in diverse neurodegenerative disorders, and would be of clinical utility for neuropathological investigations of PSP.
Objectives
To explore the usefulness of [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET in assessing characteristic distributions of tau pathologies and their association with clinical symptoms in the brains of living PSP patients.
Methods
We assessed 13 PSP patients and 13 age‐matched healthy control subjects. Individuals negative for amyloid β PET with [11C]Pittsburgh compound B underwent clinical scoring, MR scans, and [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET.
Results
There were significant differences in binding potential for [11C]pyridinyl‐butadienyl‐benzothiazole 3 between PSP patients and healthy control subjects (P = 0.02). PSP patients exhibited greater radioligand retention than healthy control subjects in multiple brain regions, including frontoparietal white matter, parietal gray matter, globus pallidus, STN, red nucleus, and cerebellar dentate nucleus. [11C]pyridinyl‐butadienyl‐benzothiazole 3 deposition in frontoparietal white matter, but not gray matter, was correlated with general severity of parkinsonian and PSP symptoms, whereas both gray matter and white matter [11C]pyridinyl‐butadienyl‐benzothiazole 3 accumulations in the frontoparietal cortices were associated with nonverbal cognitive impairments. Autoradiographic and fluorescence labeling with pyridinyl‐butadienyl‐benzothiazole 3 was observed in gray matter and white matter of PSP motor cortex tissues.
Conclusions
Our findings support the in vivo detectability of tau fibrils characteristic of PSP by [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET, and imply distinct and synergistic contributions of gray matter and white matte tau pathologies to clinical symptoms. [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET potentially provides a neuroimaging‐based index for the evolution of PSP tau pathologies promoting the deterioration of motor and cognitive functions. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</description><identifier>ISSN: 0885-3185</identifier><identifier>EISSN: 1531-8257</identifier><identifier>DOI: 10.1002/mds.27643</identifier><identifier>PMID: 30892739</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Aged ; Aged, 80 and over ; Amyloid ; Aniline Compounds ; Autoradiography ; Basal ganglia ; Benzothiazole ; Benzothiazoles ; Brain - diagnostic imaging ; Brain - metabolism ; Carbon Radioisotopes ; Case-Control Studies ; Central nervous system diseases ; Cerebellum ; Cognitive ability ; Cortex (motor) ; Dentate nucleus ; Female ; Fibrils ; Globus pallidus ; Humans ; imaging ; Male ; Middle Aged ; Movement disorders ; Neurodegenerative diseases ; Neuroimaging ; Paralysis ; Positron emission tomography ; Progressive supranuclear palsy ; Red nucleus ; Solitary tract nucleus ; Substantia alba ; Substantia grisea ; Supranuclear Palsy, Progressive - diagnostic imaging ; tau ; tau imaging ; Tau protein ; tau Proteins - metabolism ; Thiazoles</subject><ispartof>Movement disorders, 2019-05, Vol.34 (5), p.744-754</ispartof><rights>2019 The Authors. published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</rights><rights>2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</rights><rights>2019 International Parkinson and Movement Disorder Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4873-b3a3f56c3db0b8232503290309e8dec4ed454f5c3e3250931f14712cbce752b43</citedby><cites>FETCH-LOGICAL-c4873-b3a3f56c3db0b8232503290309e8dec4ed454f5c3e3250931f14712cbce752b43</cites><orcidid>0000-0001-8868-9700</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmds.27643$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmds.27643$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30892739$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Endo, Hironobu</creatorcontrib><creatorcontrib>Shimada, Hitoshi</creatorcontrib><creatorcontrib>Sahara, Naruhiko</creatorcontrib><creatorcontrib>Ono, Maiko</creatorcontrib><creatorcontrib>Koga, Shunsuke</creatorcontrib><creatorcontrib>Kitamura, Soichiro</creatorcontrib><creatorcontrib>Niwa, Fumitoshi</creatorcontrib><creatorcontrib>Hirano, Shigeki</creatorcontrib><creatorcontrib>Kimura, Yasuyuki</creatorcontrib><creatorcontrib>Ichise, Masanori</creatorcontrib><creatorcontrib>Shinotoh, Hitoshi</creatorcontrib><creatorcontrib>Zhang, Ming Rong</creatorcontrib><creatorcontrib>Kuwabara, Satoshi</creatorcontrib><creatorcontrib>Dickson, Dennis W.</creatorcontrib><creatorcontrib>Toda, Tatsushi</creatorcontrib><creatorcontrib>Suhara, Tetsuya</creatorcontrib><creatorcontrib>Higuchi, Makoto</creatorcontrib><title>In vivo binding of a tau imaging probe, [11C]PBB3, in patients with progressive supranuclear palsy</title><title>Movement disorders</title><addtitle>Mov Disord</addtitle><description>Background
[11C]pyridinyl‐butadienyl‐benzothiazole 3 is a PET imaging agent designed for capturing pathological tau aggregates in diverse neurodegenerative disorders, and would be of clinical utility for neuropathological investigations of PSP.
Objectives
To explore the usefulness of [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET in assessing characteristic distributions of tau pathologies and their association with clinical symptoms in the brains of living PSP patients.
Methods
We assessed 13 PSP patients and 13 age‐matched healthy control subjects. Individuals negative for amyloid β PET with [11C]Pittsburgh compound B underwent clinical scoring, MR scans, and [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET.
Results
There were significant differences in binding potential for [11C]pyridinyl‐butadienyl‐benzothiazole 3 between PSP patients and healthy control subjects (P = 0.02). PSP patients exhibited greater radioligand retention than healthy control subjects in multiple brain regions, including frontoparietal white matter, parietal gray matter, globus pallidus, STN, red nucleus, and cerebellar dentate nucleus. [11C]pyridinyl‐butadienyl‐benzothiazole 3 deposition in frontoparietal white matter, but not gray matter, was correlated with general severity of parkinsonian and PSP symptoms, whereas both gray matter and white matter [11C]pyridinyl‐butadienyl‐benzothiazole 3 accumulations in the frontoparietal cortices were associated with nonverbal cognitive impairments. Autoradiographic and fluorescence labeling with pyridinyl‐butadienyl‐benzothiazole 3 was observed in gray matter and white matter of PSP motor cortex tissues.
Conclusions
Our findings support the in vivo detectability of tau fibrils characteristic of PSP by [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET, and imply distinct and synergistic contributions of gray matter and white matte tau pathologies to clinical symptoms. [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET potentially provides a neuroimaging‐based index for the evolution of PSP tau pathologies promoting the deterioration of motor and cognitive functions. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amyloid</subject><subject>Aniline Compounds</subject><subject>Autoradiography</subject><subject>Basal ganglia</subject><subject>Benzothiazole</subject><subject>Benzothiazoles</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - metabolism</subject><subject>Carbon Radioisotopes</subject><subject>Case-Control Studies</subject><subject>Central nervous system diseases</subject><subject>Cerebellum</subject><subject>Cognitive ability</subject><subject>Cortex (motor)</subject><subject>Dentate nucleus</subject><subject>Female</subject><subject>Fibrils</subject><subject>Globus pallidus</subject><subject>Humans</subject><subject>imaging</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Movement disorders</subject><subject>Neurodegenerative diseases</subject><subject>Neuroimaging</subject><subject>Paralysis</subject><subject>Positron emission tomography</subject><subject>Progressive supranuclear palsy</subject><subject>Red nucleus</subject><subject>Solitary tract nucleus</subject><subject>Substantia alba</subject><subject>Substantia grisea</subject><subject>Supranuclear Palsy, Progressive - diagnostic imaging</subject><subject>tau</subject><subject>tau imaging</subject><subject>Tau protein</subject><subject>tau Proteins - metabolism</subject><subject>Thiazoles</subject><issn>0885-3185</issn><issn>1531-8257</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kU9r3DAQxUVISbbbHvIFgiCXFuJE0lhr-RJotv8CKQm0PZUiJFneKHglV7I37Lev3E1DW-hhGJj58XgzD6EjSs4oIex83aQzVi1K2EMzyoEWgvFqH82IELwAKvghep7SPSGUcro4QIdARM0qqGdIX3m8cZuAtfON8yscWqzwoEbs1mo1DfoYtD3F3yhdfr-9vIRT7Dzu1eCsHxJ-cMPdhKyiTcltLE5jH5UfTWdVzFiXti_QszZ3-_Kxz9HX9---LD8W1zcfrpZvrgtTigoKDQpavjDQaKIFA8YJsJoAqa1orCltU_Ky5QbstKqBtrSsKDPa2IozXcIcXex0-1GvbWOyv6g62cd8SdzKoJz8e-PdnVyFjVzwGkSuOXr1KBDDj9GmQa5dMrbrlLdhTJLRuuT5cTChJ_-g92GMPp8nGWOcZWsAmXq9o0wMKUXbPpmhRE7JyZyc_JVcZo__dP9E_o4qA-c74MF1dvt_Jfnp7eed5E9sj6H2</recordid><startdate>201905</startdate><enddate>201905</enddate><creator>Endo, Hironobu</creator><creator>Shimada, Hitoshi</creator><creator>Sahara, Naruhiko</creator><creator>Ono, Maiko</creator><creator>Koga, Shunsuke</creator><creator>Kitamura, Soichiro</creator><creator>Niwa, Fumitoshi</creator><creator>Hirano, Shigeki</creator><creator>Kimura, Yasuyuki</creator><creator>Ichise, Masanori</creator><creator>Shinotoh, Hitoshi</creator><creator>Zhang, Ming Rong</creator><creator>Kuwabara, Satoshi</creator><creator>Dickson, Dennis W.</creator><creator>Toda, Tatsushi</creator><creator>Suhara, Tetsuya</creator><creator>Higuchi, Makoto</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8868-9700</orcidid></search><sort><creationdate>201905</creationdate><title>In vivo binding of a tau imaging probe, [11C]PBB3, in patients with progressive supranuclear palsy</title><author>Endo, Hironobu ; Shimada, Hitoshi ; Sahara, Naruhiko ; Ono, Maiko ; Koga, Shunsuke ; Kitamura, Soichiro ; Niwa, Fumitoshi ; Hirano, Shigeki ; Kimura, Yasuyuki ; Ichise, Masanori ; Shinotoh, Hitoshi ; Zhang, Ming Rong ; Kuwabara, Satoshi ; Dickson, Dennis W. ; Toda, Tatsushi ; Suhara, Tetsuya ; Higuchi, Makoto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4873-b3a3f56c3db0b8232503290309e8dec4ed454f5c3e3250931f14712cbce752b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Amyloid</topic><topic>Aniline Compounds</topic><topic>Autoradiography</topic><topic>Basal ganglia</topic><topic>Benzothiazole</topic><topic>Benzothiazoles</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - metabolism</topic><topic>Carbon Radioisotopes</topic><topic>Case-Control Studies</topic><topic>Central nervous system diseases</topic><topic>Cerebellum</topic><topic>Cognitive ability</topic><topic>Cortex (motor)</topic><topic>Dentate nucleus</topic><topic>Female</topic><topic>Fibrils</topic><topic>Globus pallidus</topic><topic>Humans</topic><topic>imaging</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Movement disorders</topic><topic>Neurodegenerative diseases</topic><topic>Neuroimaging</topic><topic>Paralysis</topic><topic>Positron emission tomography</topic><topic>Progressive supranuclear palsy</topic><topic>Red nucleus</topic><topic>Solitary tract nucleus</topic><topic>Substantia alba</topic><topic>Substantia grisea</topic><topic>Supranuclear Palsy, Progressive - diagnostic imaging</topic><topic>tau</topic><topic>tau imaging</topic><topic>Tau protein</topic><topic>tau Proteins - metabolism</topic><topic>Thiazoles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Endo, Hironobu</creatorcontrib><creatorcontrib>Shimada, Hitoshi</creatorcontrib><creatorcontrib>Sahara, Naruhiko</creatorcontrib><creatorcontrib>Ono, Maiko</creatorcontrib><creatorcontrib>Koga, Shunsuke</creatorcontrib><creatorcontrib>Kitamura, Soichiro</creatorcontrib><creatorcontrib>Niwa, Fumitoshi</creatorcontrib><creatorcontrib>Hirano, Shigeki</creatorcontrib><creatorcontrib>Kimura, Yasuyuki</creatorcontrib><creatorcontrib>Ichise, Masanori</creatorcontrib><creatorcontrib>Shinotoh, Hitoshi</creatorcontrib><creatorcontrib>Zhang, Ming Rong</creatorcontrib><creatorcontrib>Kuwabara, Satoshi</creatorcontrib><creatorcontrib>Dickson, Dennis W.</creatorcontrib><creatorcontrib>Toda, Tatsushi</creatorcontrib><creatorcontrib>Suhara, Tetsuya</creatorcontrib><creatorcontrib>Higuchi, Makoto</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Movement disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Endo, Hironobu</au><au>Shimada, Hitoshi</au><au>Sahara, Naruhiko</au><au>Ono, Maiko</au><au>Koga, Shunsuke</au><au>Kitamura, Soichiro</au><au>Niwa, Fumitoshi</au><au>Hirano, Shigeki</au><au>Kimura, Yasuyuki</au><au>Ichise, Masanori</au><au>Shinotoh, Hitoshi</au><au>Zhang, Ming Rong</au><au>Kuwabara, Satoshi</au><au>Dickson, Dennis W.</au><au>Toda, Tatsushi</au><au>Suhara, Tetsuya</au><au>Higuchi, Makoto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo binding of a tau imaging probe, [11C]PBB3, in patients with progressive supranuclear palsy</atitle><jtitle>Movement disorders</jtitle><addtitle>Mov Disord</addtitle><date>2019-05</date><risdate>2019</risdate><volume>34</volume><issue>5</issue><spage>744</spage><epage>754</epage><pages>744-754</pages><issn>0885-3185</issn><eissn>1531-8257</eissn><abstract>Background
[11C]pyridinyl‐butadienyl‐benzothiazole 3 is a PET imaging agent designed for capturing pathological tau aggregates in diverse neurodegenerative disorders, and would be of clinical utility for neuropathological investigations of PSP.
Objectives
To explore the usefulness of [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET in assessing characteristic distributions of tau pathologies and their association with clinical symptoms in the brains of living PSP patients.
Methods
We assessed 13 PSP patients and 13 age‐matched healthy control subjects. Individuals negative for amyloid β PET with [11C]Pittsburgh compound B underwent clinical scoring, MR scans, and [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET.
Results
There were significant differences in binding potential for [11C]pyridinyl‐butadienyl‐benzothiazole 3 between PSP patients and healthy control subjects (P = 0.02). PSP patients exhibited greater radioligand retention than healthy control subjects in multiple brain regions, including frontoparietal white matter, parietal gray matter, globus pallidus, STN, red nucleus, and cerebellar dentate nucleus. [11C]pyridinyl‐butadienyl‐benzothiazole 3 deposition in frontoparietal white matter, but not gray matter, was correlated with general severity of parkinsonian and PSP symptoms, whereas both gray matter and white matter [11C]pyridinyl‐butadienyl‐benzothiazole 3 accumulations in the frontoparietal cortices were associated with nonverbal cognitive impairments. Autoradiographic and fluorescence labeling with pyridinyl‐butadienyl‐benzothiazole 3 was observed in gray matter and white matter of PSP motor cortex tissues.
Conclusions
Our findings support the in vivo detectability of tau fibrils characteristic of PSP by [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET, and imply distinct and synergistic contributions of gray matter and white matte tau pathologies to clinical symptoms. [11C]pyridinyl‐butadienyl‐benzothiazole 3/PET potentially provides a neuroimaging‐based index for the evolution of PSP tau pathologies promoting the deterioration of motor and cognitive functions. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>30892739</pmid><doi>10.1002/mds.27643</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-8868-9700</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Movement disorders, 2019-05, Vol.34 (5), p.744-754 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Aged Aged, 80 and over Amyloid Aniline Compounds Autoradiography Basal ganglia Benzothiazole Benzothiazoles Brain - diagnostic imaging Brain - metabolism Carbon Radioisotopes Case-Control Studies Central nervous system diseases Cerebellum Cognitive ability Cortex (motor) Dentate nucleus Female Fibrils Globus pallidus Humans imaging Male Middle Aged Movement disorders Neurodegenerative diseases Neuroimaging Paralysis Positron emission tomography Progressive supranuclear palsy Red nucleus Solitary tract nucleus Substantia alba Substantia grisea Supranuclear Palsy, Progressive - diagnostic imaging tau tau imaging Tau protein tau Proteins - metabolism Thiazoles |
| title | In vivo binding of a tau imaging probe, [11C]PBB3, in patients with progressive supranuclear palsy |
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