Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer ¹¹C-AZD2184
Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-β deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid senile plaques, (11)C-labeled 5-(6-{[tert-butyl(dimethyl)silyl]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine ((11)C-AZD2184), was developed, and i...
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| Veröffentlicht in: | The Journal of nuclear medicine (1978) 2014-06, Vol.55 (6), p.932-938 |
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| creator | Ito, Hiroshi Shimada, Hitoshi Shinotoh, Hitoshi Takano, Harumasa Sasaki, Takeshi Nogami, Tsuyoshi Suzuki, Masayuki Nagashima, Tomohisa Takahata, Keisuke Seki, Chie Kodaka, Fumitoshi Eguchi, Yoko Fujiwara, Hironobu Kimura, Yasuyuki Hirano, Shigeki Ikoma, Yoko Higuchi, Makoto Kawamura, Kazunori Fukumura, Toshimitsu Böö, Éva Lindström Farde, Lars Suhara, Tetsuya |
| description | Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-β deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid senile plaques, (11)C-labeled 5-(6-{[tert-butyl(dimethyl)silyl]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine ((11)C-AZD2184), was developed, and it was reported to show rapid brain uptake followed by rapid washout. In this study, (11)C-AZD2184 binding in control subjects and AD patients was examined in more detail by compartment model analysis using a metabolite-corrected arterial input function. The accuracy of simplified quantitative methods using a reference brain region was also evaluated.
After intravenous bolus injection of (11)C-AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and high-performance liquid chromatography analysis were performed.
Time-activity curves in all brain regions could be described using the standard 2-tissue-compartment model. The total distribution volume ratios to reference region (DVR) in cerebral cortical regions were significantly higher in AD patients than in control subjects. Although there was no conspicuous accumulation of radioactivity in white matter as compared with other amyloid radioligands, DVR values in the centrum semiovale were more than 1 for both control subjects and AD patients, suggesting binding to myelin. The standardized uptake value ratio calculated from integrated time-activity curves in brain regions and the reference region was statistically in good agreement with DVR.
Although the white matter binding of (11)C-AZD2184 may have some effect on cortical measurement, it can be concluded that the kinetic behavior of (11)C-AZD2184 is suitable for quantitative analysis. The standardized uptake value ratio can be used as a validated measure of (11)C-AZD2184 binding in clinical examinations without arterial input function. |
| doi_str_mv | 10.2967/jnumed.113.133793 |
| format | Article |
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After intravenous bolus injection of (11)C-AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and high-performance liquid chromatography analysis were performed.
Time-activity curves in all brain regions could be described using the standard 2-tissue-compartment model. The total distribution volume ratios to reference region (DVR) in cerebral cortical regions were significantly higher in AD patients than in control subjects. Although there was no conspicuous accumulation of radioactivity in white matter as compared with other amyloid radioligands, DVR values in the centrum semiovale were more than 1 for both control subjects and AD patients, suggesting binding to myelin. The standardized uptake value ratio calculated from integrated time-activity curves in brain regions and the reference region was statistically in good agreement with DVR.
Although the white matter binding of (11)C-AZD2184 may have some effect on cortical measurement, it can be concluded that the kinetic behavior of (11)C-AZD2184 is suitable for quantitative analysis. The standardized uptake value ratio can be used as a validated measure of (11)C-AZD2184 binding in clinical examinations without arterial input function.</description><identifier>ISSN: 0161-5505</identifier><identifier>EISSN: 1535-5667</identifier><identifier>DOI: 10.2967/jnumed.113.133793</identifier><identifier>PMID: 24732152</identifier><language>eng</language><publisher>United States</publisher><subject>Aged ; Aged, 80 and over ; Alzheimer Disease - diagnostic imaging ; Alzheimer Disease - metabolism ; Alzheimer Disease - physiopathology ; Aminopyridines - metabolism ; Amyloid - metabolism ; Arteries - physiopathology ; Benzothiazoles - metabolism ; Female ; Humans ; Kinetics ; Male ; Middle Aged ; Models, Biological ; Positron-Emission Tomography</subject><ispartof>The Journal of nuclear medicine (1978), 2014-06, Vol.55 (6), p.932-938</ispartof><rights>2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24732152$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ito, Hiroshi</creatorcontrib><creatorcontrib>Shimada, Hitoshi</creatorcontrib><creatorcontrib>Shinotoh, Hitoshi</creatorcontrib><creatorcontrib>Takano, Harumasa</creatorcontrib><creatorcontrib>Sasaki, Takeshi</creatorcontrib><creatorcontrib>Nogami, Tsuyoshi</creatorcontrib><creatorcontrib>Suzuki, Masayuki</creatorcontrib><creatorcontrib>Nagashima, Tomohisa</creatorcontrib><creatorcontrib>Takahata, Keisuke</creatorcontrib><creatorcontrib>Seki, Chie</creatorcontrib><creatorcontrib>Kodaka, Fumitoshi</creatorcontrib><creatorcontrib>Eguchi, Yoko</creatorcontrib><creatorcontrib>Fujiwara, Hironobu</creatorcontrib><creatorcontrib>Kimura, Yasuyuki</creatorcontrib><creatorcontrib>Hirano, Shigeki</creatorcontrib><creatorcontrib>Ikoma, Yoko</creatorcontrib><creatorcontrib>Higuchi, Makoto</creatorcontrib><creatorcontrib>Kawamura, Kazunori</creatorcontrib><creatorcontrib>Fukumura, Toshimitsu</creatorcontrib><creatorcontrib>Böö, Éva Lindström</creatorcontrib><creatorcontrib>Farde, Lars</creatorcontrib><creatorcontrib>Suhara, Tetsuya</creatorcontrib><title>Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer ¹¹C-AZD2184</title><title>The Journal of nuclear medicine (1978)</title><addtitle>J Nucl Med</addtitle><description>Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-β deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid senile plaques, (11)C-labeled 5-(6-{[tert-butyl(dimethyl)silyl]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine ((11)C-AZD2184), was developed, and it was reported to show rapid brain uptake followed by rapid washout. In this study, (11)C-AZD2184 binding in control subjects and AD patients was examined in more detail by compartment model analysis using a metabolite-corrected arterial input function. The accuracy of simplified quantitative methods using a reference brain region was also evaluated.
After intravenous bolus injection of (11)C-AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and high-performance liquid chromatography analysis were performed.
Time-activity curves in all brain regions could be described using the standard 2-tissue-compartment model. The total distribution volume ratios to reference region (DVR) in cerebral cortical regions were significantly higher in AD patients than in control subjects. Although there was no conspicuous accumulation of radioactivity in white matter as compared with other amyloid radioligands, DVR values in the centrum semiovale were more than 1 for both control subjects and AD patients, suggesting binding to myelin. The standardized uptake value ratio calculated from integrated time-activity curves in brain regions and the reference region was statistically in good agreement with DVR.
Although the white matter binding of (11)C-AZD2184 may have some effect on cortical measurement, it can be concluded that the kinetic behavior of (11)C-AZD2184 is suitable for quantitative analysis. The standardized uptake value ratio can be used as a validated measure of (11)C-AZD2184 binding in clinical examinations without arterial input function.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - diagnostic imaging</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer Disease - physiopathology</subject><subject>Aminopyridines - metabolism</subject><subject>Amyloid - metabolism</subject><subject>Arteries - physiopathology</subject><subject>Benzothiazoles - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Models, Biological</subject><subject>Positron-Emission Tomography</subject><issn>0161-5505</issn><issn>1535-5667</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0LtOwzAYhmELgWg5XAAL8siS4rOdMWrLQarEQe3CEjnJH-oqhxI7SOXOuvbKKKLMTN_y6BtehK4oGbFY6dtV09dQjCjlI8q5jvkRGlLJZSSV0sdoSKiikZREDtCZ9ytCiDLGnKIBE5ozKtkQVS-9bYILNrhPwEljq413HrclTupN1boCT2Ddehdc22DX4KT6WoKrocMT58F6wAvvmnf8PJ1j2xQ4LAG_2sK1obP5Xu22u-04St4mjBpxgU5KW3m4POw5WtxN5-OHaPZ0_zhOZtGKMx0iClZkQipGSqKUjQWA4EVBmGAmy41VBdCYGKmJogbyOLdSZ5lgUhsQZQb8HN38_q679qMHH9La-RyqyjbQ9j6lSmtjhCb0fyolVVxp9UOvD7TP9tnTdedq223Sv5j8G1j_d78</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Ito, Hiroshi</creator><creator>Shimada, Hitoshi</creator><creator>Shinotoh, Hitoshi</creator><creator>Takano, Harumasa</creator><creator>Sasaki, Takeshi</creator><creator>Nogami, Tsuyoshi</creator><creator>Suzuki, Masayuki</creator><creator>Nagashima, Tomohisa</creator><creator>Takahata, Keisuke</creator><creator>Seki, Chie</creator><creator>Kodaka, Fumitoshi</creator><creator>Eguchi, Yoko</creator><creator>Fujiwara, Hironobu</creator><creator>Kimura, Yasuyuki</creator><creator>Hirano, Shigeki</creator><creator>Ikoma, Yoko</creator><creator>Higuchi, Makoto</creator><creator>Kawamura, Kazunori</creator><creator>Fukumura, Toshimitsu</creator><creator>Böö, Éva Lindström</creator><creator>Farde, Lars</creator><creator>Suhara, Tetsuya</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20140601</creationdate><title>Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer ¹¹C-AZD2184</title><author>Ito, Hiroshi ; 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Recently, a new radioligand for amyloid senile plaques, (11)C-labeled 5-(6-{[tert-butyl(dimethyl)silyl]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine ((11)C-AZD2184), was developed, and it was reported to show rapid brain uptake followed by rapid washout. In this study, (11)C-AZD2184 binding in control subjects and AD patients was examined in more detail by compartment model analysis using a metabolite-corrected arterial input function. The accuracy of simplified quantitative methods using a reference brain region was also evaluated.
After intravenous bolus injection of (11)C-AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and high-performance liquid chromatography analysis were performed.
Time-activity curves in all brain regions could be described using the standard 2-tissue-compartment model. The total distribution volume ratios to reference region (DVR) in cerebral cortical regions were significantly higher in AD patients than in control subjects. Although there was no conspicuous accumulation of radioactivity in white matter as compared with other amyloid radioligands, DVR values in the centrum semiovale were more than 1 for both control subjects and AD patients, suggesting binding to myelin. The standardized uptake value ratio calculated from integrated time-activity curves in brain regions and the reference region was statistically in good agreement with DVR.
Although the white matter binding of (11)C-AZD2184 may have some effect on cortical measurement, it can be concluded that the kinetic behavior of (11)C-AZD2184 is suitable for quantitative analysis. The standardized uptake value ratio can be used as a validated measure of (11)C-AZD2184 binding in clinical examinations without arterial input function.</abstract><cop>United States</cop><pmid>24732152</pmid><doi>10.2967/jnumed.113.133793</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Alzheimer Disease - diagnostic imaging Alzheimer Disease - metabolism Alzheimer Disease - physiopathology Aminopyridines - metabolism Amyloid - metabolism Arteries - physiopathology Benzothiazoles - metabolism Female Humans Kinetics Male Middle Aged Models, Biological Positron-Emission Tomography |
| title | Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer ¹¹C-AZD2184 |
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