PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans
Purpose The α 7 nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α 7 nAChRs PET radioligands, [ 18 F]ASEM (3-(1,4-diazabicyclo[3.2.2]n...
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| Veröffentlicht in: | European journal of nuclear medicine and molecular imaging 2017-06, Vol.44 (6), p.1042-1050 |
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| creator | Hillmer, Ansel T. Li, Songye Zheng, Ming-Qiang Scheunemann, Matthias Lin, Shu-fei Nabulsi, Nabeel Holden, Daniel Pracitto, Richard Labaree, David Ropchan, Jim Teodoro, Rodrigo Deuther-Conrad, Winnie Esterlis, Irina Cosgrove, Kelly P. Brust, Peter Carson, Richard E. Huang, Yiyun |
| description | Purpose
The α
7
nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α
7
nAChRs PET radioligands, [
18
F]ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([
18
F]fluorodibenzo[
b,d
]thiophene 5,5-dioxide) and [
18
F]DBT-10 (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([
18
F]fluorodibenzo[
b,d
]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [
18
F]ASEM in humans.
Methods
PET scans with high specific activity [
18
F]ASEM or [
18
F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [
18
F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [
18
F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [
18
F]ASEM distribution volume (
V
T
). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of
V
T
was assessed.
Results
In the rhesus monkey brain [
18
F]ASEM and [
18
F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [
18
F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [
18
F]ASEM
V
T
. [
18
F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [
18
F]ASEM
V
T
in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in
V
T
values ranging from 19.6 ± 2.5 mL/cm
3
in cerebellum to 25.9 ± 2.9 mL/cm
3
in thalamus. Test-retest variability of
V
T
was 11.7 ± 9.8%.
Conclusions
These results confirm [
18
F]ASEM as a suitable radiotracer for the imaging and quantification of α
7
nAChRs in humans. |
| doi_str_mv | 10.1007/s00259-017-3621-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1861868105</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1861868105</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3458-6c88aa74578141a330289f687f3693131821fef23fc6c56ed2eeadc20c8649403</originalsourceid><addsrcrecordid>eNp9kc1KxDAUhYsoOI4-gLssXVjNbdo0defP-AOKguNKJITMzUylk4xJK8wrufNFfCYzUxHcCOEmF853wuEkyT7QI6C0PA6UZkWVUihTxjNIxUYyAA5VWlJRbf6-S7qd7ITwSimITFSD5ONhNCb1XE1rOyXOkK_Pkthau7aOkyiN7bLRM9fUFolHjYvW-XBCFNFuvlBetfU7ktB2k-WKfgZx-XL6OLojyk767eJsnAIltSXW2Vk3V5YsfPywxXC4VpnOtzP0BN9V00U_Z_86RXKNhd1ky6gm4N7PPUyeLkfj8-v09v7q5vz0NtUsL0TKtRBKlXlRCshBMUZjUMNFaRivGLAYHAyajBnNdcFxkiGqic6oFjyvcsqGyUHvu_DurcPQynkdNDaNsui6IEHweATQIkqhl2rvQvBo5DqbX0qgctWL7HuRsRe56kWKyGQ9E6LWTtHLV9d5GxP9A30DxRmP3g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1861868105</pqid></control><display><type>article</type><title>PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans</title><source>SpringerLink Journals - AutoHoldings</source><creator>Hillmer, Ansel T. ; Li, Songye ; Zheng, Ming-Qiang ; Scheunemann, Matthias ; Lin, Shu-fei ; Nabulsi, Nabeel ; Holden, Daniel ; Pracitto, Richard ; Labaree, David ; Ropchan, Jim ; Teodoro, Rodrigo ; Deuther-Conrad, Winnie ; Esterlis, Irina ; Cosgrove, Kelly P. ; Brust, Peter ; Carson, Richard E. ; Huang, Yiyun</creator><creatorcontrib>Hillmer, Ansel T. ; Li, Songye ; Zheng, Ming-Qiang ; Scheunemann, Matthias ; Lin, Shu-fei ; Nabulsi, Nabeel ; Holden, Daniel ; Pracitto, Richard ; Labaree, David ; Ropchan, Jim ; Teodoro, Rodrigo ; Deuther-Conrad, Winnie ; Esterlis, Irina ; Cosgrove, Kelly P. ; Brust, Peter ; Carson, Richard E. ; Huang, Yiyun</creatorcontrib><description>Purpose
The α
7
nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α
7
nAChRs PET radioligands, [
18
F]ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([
18
F]fluorodibenzo[
b,d
]thiophene 5,5-dioxide) and [
18
F]DBT-10 (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([
18
F]fluorodibenzo[
b,d
]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [
18
F]ASEM in humans.
Methods
PET scans with high specific activity [
18
F]ASEM or [
18
F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [
18
F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [
18
F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [
18
F]ASEM distribution volume (
V
T
). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of
V
T
was assessed.
Results
In the rhesus monkey brain [
18
F]ASEM and [
18
F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [
18
F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [
18
F]ASEM
V
T
. [
18
F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [
18
F]ASEM
V
T
in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in
V
T
values ranging from 19.6 ± 2.5 mL/cm
3
in cerebellum to 25.9 ± 2.9 mL/cm
3
in thalamus. Test-retest variability of
V
T
was 11.7 ± 9.8%.
Conclusions
These results confirm [
18
F]ASEM as a suitable radiotracer for the imaging and quantification of α
7
nAChRs in humans.</description><identifier>ISSN: 1619-7070</identifier><identifier>EISSN: 1619-7089</identifier><identifier>DOI: 10.1007/s00259-017-3621-8</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Cardiology ; Imaging ; Medicine ; Medicine & Public Health ; Nuclear Medicine ; Oncology ; Original Article ; Orthopedics ; Radiology</subject><ispartof>European journal of nuclear medicine and molecular imaging, 2017-06, Vol.44 (6), p.1042-1050</ispartof><rights>Springer-Verlag Berlin Heidelberg 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3458-6c88aa74578141a330289f687f3693131821fef23fc6c56ed2eeadc20c8649403</citedby><cites>FETCH-LOGICAL-c3458-6c88aa74578141a330289f687f3693131821fef23fc6c56ed2eeadc20c8649403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00259-017-3621-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00259-017-3621-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27922,27923,41486,42555,51317</link.rule.ids></links><search><creatorcontrib>Hillmer, Ansel T.</creatorcontrib><creatorcontrib>Li, Songye</creatorcontrib><creatorcontrib>Zheng, Ming-Qiang</creatorcontrib><creatorcontrib>Scheunemann, Matthias</creatorcontrib><creatorcontrib>Lin, Shu-fei</creatorcontrib><creatorcontrib>Nabulsi, Nabeel</creatorcontrib><creatorcontrib>Holden, Daniel</creatorcontrib><creatorcontrib>Pracitto, Richard</creatorcontrib><creatorcontrib>Labaree, David</creatorcontrib><creatorcontrib>Ropchan, Jim</creatorcontrib><creatorcontrib>Teodoro, Rodrigo</creatorcontrib><creatorcontrib>Deuther-Conrad, Winnie</creatorcontrib><creatorcontrib>Esterlis, Irina</creatorcontrib><creatorcontrib>Cosgrove, Kelly P.</creatorcontrib><creatorcontrib>Brust, Peter</creatorcontrib><creatorcontrib>Carson, Richard E.</creatorcontrib><creatorcontrib>Huang, Yiyun</creatorcontrib><title>PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans</title><title>European journal of nuclear medicine and molecular imaging</title><addtitle>Eur J Nucl Med Mol Imaging</addtitle><description>Purpose
The α
7
nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α
7
nAChRs PET radioligands, [
18
F]ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([
18
F]fluorodibenzo[
b,d
]thiophene 5,5-dioxide) and [
18
F]DBT-10 (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([
18
F]fluorodibenzo[
b,d
]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [
18
F]ASEM in humans.
Methods
PET scans with high specific activity [
18
F]ASEM or [
18
F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [
18
F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [
18
F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [
18
F]ASEM distribution volume (
V
T
). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of
V
T
was assessed.
Results
In the rhesus monkey brain [
18
F]ASEM and [
18
F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [
18
F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [
18
F]ASEM
V
T
. [
18
F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [
18
F]ASEM
V
T
in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in
V
T
values ranging from 19.6 ± 2.5 mL/cm
3
in cerebellum to 25.9 ± 2.9 mL/cm
3
in thalamus. Test-retest variability of
V
T
was 11.7 ± 9.8%.
Conclusions
These results confirm [
18
F]ASEM as a suitable radiotracer for the imaging and quantification of α
7
nAChRs in humans.</description><subject>Cardiology</subject><subject>Imaging</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Nuclear Medicine</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Radiology</subject><issn>1619-7070</issn><issn>1619-7089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp9kc1KxDAUhYsoOI4-gLssXVjNbdo0defP-AOKguNKJITMzUylk4xJK8wrufNFfCYzUxHcCOEmF853wuEkyT7QI6C0PA6UZkWVUihTxjNIxUYyAA5VWlJRbf6-S7qd7ITwSimITFSD5ONhNCb1XE1rOyXOkK_Pkthau7aOkyiN7bLRM9fUFolHjYvW-XBCFNFuvlBetfU7ktB2k-WKfgZx-XL6OLojyk767eJsnAIltSXW2Vk3V5YsfPywxXC4VpnOtzP0BN9V00U_Z_86RXKNhd1ky6gm4N7PPUyeLkfj8-v09v7q5vz0NtUsL0TKtRBKlXlRCshBMUZjUMNFaRivGLAYHAyajBnNdcFxkiGqic6oFjyvcsqGyUHvu_DurcPQynkdNDaNsui6IEHweATQIkqhl2rvQvBo5DqbX0qgctWL7HuRsRe56kWKyGQ9E6LWTtHLV9d5GxP9A30DxRmP3g</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Hillmer, Ansel T.</creator><creator>Li, Songye</creator><creator>Zheng, Ming-Qiang</creator><creator>Scheunemann, Matthias</creator><creator>Lin, Shu-fei</creator><creator>Nabulsi, Nabeel</creator><creator>Holden, Daniel</creator><creator>Pracitto, Richard</creator><creator>Labaree, David</creator><creator>Ropchan, Jim</creator><creator>Teodoro, Rodrigo</creator><creator>Deuther-Conrad, Winnie</creator><creator>Esterlis, Irina</creator><creator>Cosgrove, Kelly P.</creator><creator>Brust, Peter</creator><creator>Carson, Richard E.</creator><creator>Huang, Yiyun</creator><general>Springer Berlin Heidelberg</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20170601</creationdate><title>PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans</title><author>Hillmer, Ansel T. ; Li, Songye ; Zheng, Ming-Qiang ; Scheunemann, Matthias ; Lin, Shu-fei ; Nabulsi, Nabeel ; Holden, Daniel ; Pracitto, Richard ; Labaree, David ; Ropchan, Jim ; Teodoro, Rodrigo ; Deuther-Conrad, Winnie ; Esterlis, Irina ; Cosgrove, Kelly P. ; Brust, Peter ; Carson, Richard E. ; Huang, Yiyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3458-6c88aa74578141a330289f687f3693131821fef23fc6c56ed2eeadc20c8649403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Cardiology</topic><topic>Imaging</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Nuclear Medicine</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Radiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hillmer, Ansel T.</creatorcontrib><creatorcontrib>Li, Songye</creatorcontrib><creatorcontrib>Zheng, Ming-Qiang</creatorcontrib><creatorcontrib>Scheunemann, Matthias</creatorcontrib><creatorcontrib>Lin, Shu-fei</creatorcontrib><creatorcontrib>Nabulsi, Nabeel</creatorcontrib><creatorcontrib>Holden, Daniel</creatorcontrib><creatorcontrib>Pracitto, Richard</creatorcontrib><creatorcontrib>Labaree, David</creatorcontrib><creatorcontrib>Ropchan, Jim</creatorcontrib><creatorcontrib>Teodoro, Rodrigo</creatorcontrib><creatorcontrib>Deuther-Conrad, Winnie</creatorcontrib><creatorcontrib>Esterlis, Irina</creatorcontrib><creatorcontrib>Cosgrove, Kelly P.</creatorcontrib><creatorcontrib>Brust, Peter</creatorcontrib><creatorcontrib>Carson, Richard E.</creatorcontrib><creatorcontrib>Huang, Yiyun</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of nuclear medicine and molecular imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hillmer, Ansel T.</au><au>Li, Songye</au><au>Zheng, Ming-Qiang</au><au>Scheunemann, Matthias</au><au>Lin, Shu-fei</au><au>Nabulsi, Nabeel</au><au>Holden, Daniel</au><au>Pracitto, Richard</au><au>Labaree, David</au><au>Ropchan, Jim</au><au>Teodoro, Rodrigo</au><au>Deuther-Conrad, Winnie</au><au>Esterlis, Irina</au><au>Cosgrove, Kelly P.</au><au>Brust, Peter</au><au>Carson, Richard E.</au><au>Huang, Yiyun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans</atitle><jtitle>European journal of nuclear medicine and molecular imaging</jtitle><stitle>Eur J Nucl Med Mol Imaging</stitle><date>2017-06-01</date><risdate>2017</risdate><volume>44</volume><issue>6</issue><spage>1042</spage><epage>1050</epage><pages>1042-1050</pages><issn>1619-7070</issn><eissn>1619-7089</eissn><abstract>Purpose
The α
7
nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α
7
nAChRs PET radioligands, [
18
F]ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([
18
F]fluorodibenzo[
b,d
]thiophene 5,5-dioxide) and [
18
F]DBT-10 (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([
18
F]fluorodibenzo[
b,d
]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [
18
F]ASEM in humans.
Methods
PET scans with high specific activity [
18
F]ASEM or [
18
F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [
18
F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [
18
F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [
18
F]ASEM distribution volume (
V
T
). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of
V
T
was assessed.
Results
In the rhesus monkey brain [
18
F]ASEM and [
18
F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [
18
F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [
18
F]ASEM
V
T
. [
18
F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [
18
F]ASEM
V
T
in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in
V
T
values ranging from 19.6 ± 2.5 mL/cm
3
in cerebellum to 25.9 ± 2.9 mL/cm
3
in thalamus. Test-retest variability of
V
T
was 11.7 ± 9.8%.
Conclusions
These results confirm [
18
F]ASEM as a suitable radiotracer for the imaging and quantification of α
7
nAChRs in humans.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><doi>10.1007/s00259-017-3621-8</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Cardiology Imaging Medicine Medicine & Public Health Nuclear Medicine Oncology Original Article Orthopedics Radiology |
| title | PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans |
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