The P2X7 receptor tracer [11C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study
Purpose The novel PET tracer [ 11 C]SMW139 binds with high affinity to the P2X 7 receptor, which is expressed on pro-inflammatory microglia. The purposes of this first in-man study were to characterise pharmacokinetics of [ 11 C]SMW139 in patients with active relapsing remitting multiple sclerosis (...
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| Veröffentlicht in: | European journal of nuclear medicine and molecular imaging 2020-02, Vol.47 (2), p.379-389 |
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| creator | Hagens, Marloes H. J. Golla, Sandeep S. V. Janssen, Bieneke Vugts, Danielle J. Beaino, Wissam Windhorst, Albert D. O’Brien-Brown, James Kassiou, Michael Schuit, Robert C. Schwarte, Lothar A. de Vries, Helga E. Killestein, Joep Barkhof, Frederik van Berckel, Bart N. M. Lammertsma, Adriaan A. |
| description | Purpose
The novel PET tracer [
11
C]SMW139 binds with high affinity to the P2X
7
receptor, which is expressed on pro-inflammatory microglia. The purposes of this first in-man study were to characterise pharmacokinetics of [
11
C]SMW139 in patients with active relapsing remitting multiple sclerosis (RRMS) and healthy controls (HC) and to evaluate its potential to identify
in vivo
neuroinflammation in RRMS.
Methods
Five RRMS patients and 5 age-matched HC underwent 90-min dynamic [
11
C]SMW139 PET scans, with online continuous and manual arterial sampling to generate a metabolite-corrected arterial plasma input function. Tissue time activity curves were fitted to single- and two-tissue compartment models, and the model that provided the best fits was determined using the Akaike information criterion.
Results
The optimal model for describing [
11
C]SMW139 kinetics in both RRMS and HC was a reversible two-tissue compartment model with blood volume parameter and with the dissociation rate k
4
fixed to the whole-brain value. Exploratory group level comparisons demonstrated an increased volume of distribution (V
T
) and binding potential (BP
ND
) in RRMS compared with HC in normal appearing brain regions. BP
ND
in MS lesions was decreased compared with non-lesional white matter, and a further decrease was observed in gadolinium-enhancing lesions. In contrast, increased V
T
was observed in enhancing lesions, possibly resulting from disruption of the blood-brain barrier in active MS lesions. In addition, there was a high correlation between parameters obtained from 60- to 90-min datasets, although analyses using 60-min data led to a slight underestimation in regional V
T
and BP
ND
values.
Conclusions
This first in-man study demonstrated that uptake of [
11
C]SMW139 can be quantified with PET using BP
ND
as a measure for specific binding in healthy controls and RRMS patients. Additional studies are warranted for further clinical evaluation of this novel neuroinflammation tracer. |
| doi_str_mv | 10.1007/s00259-019-04550-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6974509</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2343248444</sourcerecordid><originalsourceid>FETCH-LOGICAL-c432x-6578a3700f153e3a283ed9ccde64bf39df679640ed8aa5e999e9535e6120815b3</originalsourceid><addsrcrecordid>eNp9UdFKHDEUDaK41voDPgX6PHozSSYTHwqytFqwKGhpoZSQnbnjZp2ZrMnMsvr1jbti6YsPl9xwzzn3Hg4hxwxOGIA6jQC51BmwVEJKyNY75IAV6aug1LtvvYIJ-RDjAoCVean3yYQzBZIpcUCe7-ZIb_JfigascDn4QIdgKwz0N2PTP7fffzKuqY3U9tT1dOVWnnY2PCSAb2iPY_Cub1rbdXZwfoPpxnZwyxZprFoMPrp4Ri1tXIhD9jJOSnEY66ePZK-xbcSj1_eQ_Pj65W56mV1dX3ybnl9lleD5OiukKi1XAA2THLnNS461rqoaCzFruK6bQulCANaltRK11qgll1iwHEomZ_yQfN7qLsdZh3WFfXLYmmVwyciT8daZ_ye9m5t7vzKFVkKCTgKfXgWCfxwxDmbhx9Cnm03O042iFEIkVL5FVclzDNi8bWBgXvIy27xMysts8jLrROJbUkzg_h7DP-l3WH8B5DOYDg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2343248444</pqid></control><display><type>article</type><title>The P2X7 receptor tracer [11C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study</title><source>SpringerLink Journals - AutoHoldings</source><creator>Hagens, Marloes H. J. ; Golla, Sandeep S. V. ; Janssen, Bieneke ; Vugts, Danielle J. ; Beaino, Wissam ; Windhorst, Albert D. ; O’Brien-Brown, James ; Kassiou, Michael ; Schuit, Robert C. ; Schwarte, Lothar A. ; de Vries, Helga E. ; Killestein, Joep ; Barkhof, Frederik ; van Berckel, Bart N. M. ; Lammertsma, Adriaan A.</creator><creatorcontrib>Hagens, Marloes H. J. ; Golla, Sandeep S. V. ; Janssen, Bieneke ; Vugts, Danielle J. ; Beaino, Wissam ; Windhorst, Albert D. ; O’Brien-Brown, James ; Kassiou, Michael ; Schuit, Robert C. ; Schwarte, Lothar A. ; de Vries, Helga E. ; Killestein, Joep ; Barkhof, Frederik ; van Berckel, Bart N. M. ; Lammertsma, Adriaan A.</creatorcontrib><description>Purpose
The novel PET tracer [
11
C]SMW139 binds with high affinity to the P2X
7
receptor, which is expressed on pro-inflammatory microglia. The purposes of this first in-man study were to characterise pharmacokinetics of [
11
C]SMW139 in patients with active relapsing remitting multiple sclerosis (RRMS) and healthy controls (HC) and to evaluate its potential to identify
in vivo
neuroinflammation in RRMS.
Methods
Five RRMS patients and 5 age-matched HC underwent 90-min dynamic [
11
C]SMW139 PET scans, with online continuous and manual arterial sampling to generate a metabolite-corrected arterial plasma input function. Tissue time activity curves were fitted to single- and two-tissue compartment models, and the model that provided the best fits was determined using the Akaike information criterion.
Results
The optimal model for describing [
11
C]SMW139 kinetics in both RRMS and HC was a reversible two-tissue compartment model with blood volume parameter and with the dissociation rate k
4
fixed to the whole-brain value. Exploratory group level comparisons demonstrated an increased volume of distribution (V
T
) and binding potential (BP
ND
) in RRMS compared with HC in normal appearing brain regions. BP
ND
in MS lesions was decreased compared with non-lesional white matter, and a further decrease was observed in gadolinium-enhancing lesions. In contrast, increased V
T
was observed in enhancing lesions, possibly resulting from disruption of the blood-brain barrier in active MS lesions. In addition, there was a high correlation between parameters obtained from 60- to 90-min datasets, although analyses using 60-min data led to a slight underestimation in regional V
T
and BP
ND
values.
Conclusions
This first in-man study demonstrated that uptake of [
11
C]SMW139 can be quantified with PET using BP
ND
as a measure for specific binding in healthy controls and RRMS patients. Additional studies are warranted for further clinical evaluation of this novel neuroinflammation tracer.</description><identifier>ISSN: 1619-7070</identifier><identifier>EISSN: 1619-7089</identifier><identifier>DOI: 10.1007/s00259-019-04550-x</identifier><identifier>PMID: 31705174</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Binding ; Blood volume ; Blood-brain barrier ; Cardiology ; Disruption ; Evaluation ; Gadolinium ; Imaging ; In vivo methods and tests ; Inflammation ; Lesions ; Mathematical models ; Medicine ; Medicine & Public Health ; Metabolites ; Microglia ; Multiple sclerosis ; Neurology ; Nuclear Medicine ; Oncology ; Original ; Original Article ; Orthopedics ; Parameters ; Pharmacokinetics ; Positron emission ; Positron emission tomography ; Radiology ; Substantia alba ; Tissues ; Tomography</subject><ispartof>European journal of nuclear medicine and molecular imaging, 2020-02, Vol.47 (2), p.379-389</ispartof><rights>The Author(s) 2019</rights><rights>European Journal of Nuclear Medicine and Molecular Imaging is a copyright of Springer, (2019). All Rights Reserved. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c432x-6578a3700f153e3a283ed9ccde64bf39df679640ed8aa5e999e9535e6120815b3</citedby><cites>FETCH-LOGICAL-c432x-6578a3700f153e3a283ed9ccde64bf39df679640ed8aa5e999e9535e6120815b3</cites><orcidid>0000-0002-7115-6833</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00259-019-04550-x$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00259-019-04550-x$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids></links><search><creatorcontrib>Hagens, Marloes H. J.</creatorcontrib><creatorcontrib>Golla, Sandeep S. V.</creatorcontrib><creatorcontrib>Janssen, Bieneke</creatorcontrib><creatorcontrib>Vugts, Danielle J.</creatorcontrib><creatorcontrib>Beaino, Wissam</creatorcontrib><creatorcontrib>Windhorst, Albert D.</creatorcontrib><creatorcontrib>O’Brien-Brown, James</creatorcontrib><creatorcontrib>Kassiou, Michael</creatorcontrib><creatorcontrib>Schuit, Robert C.</creatorcontrib><creatorcontrib>Schwarte, Lothar A.</creatorcontrib><creatorcontrib>de Vries, Helga E.</creatorcontrib><creatorcontrib>Killestein, Joep</creatorcontrib><creatorcontrib>Barkhof, Frederik</creatorcontrib><creatorcontrib>van Berckel, Bart N. M.</creatorcontrib><creatorcontrib>Lammertsma, Adriaan A.</creatorcontrib><title>The P2X7 receptor tracer [11C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study</title><title>European journal of nuclear medicine and molecular imaging</title><addtitle>Eur J Nucl Med Mol Imaging</addtitle><description>Purpose
The novel PET tracer [
11
C]SMW139 binds with high affinity to the P2X
7
receptor, which is expressed on pro-inflammatory microglia. The purposes of this first in-man study were to characterise pharmacokinetics of [
11
C]SMW139 in patients with active relapsing remitting multiple sclerosis (RRMS) and healthy controls (HC) and to evaluate its potential to identify
in vivo
neuroinflammation in RRMS.
Methods
Five RRMS patients and 5 age-matched HC underwent 90-min dynamic [
11
C]SMW139 PET scans, with online continuous and manual arterial sampling to generate a metabolite-corrected arterial plasma input function. Tissue time activity curves were fitted to single- and two-tissue compartment models, and the model that provided the best fits was determined using the Akaike information criterion.
Results
The optimal model for describing [
11
C]SMW139 kinetics in both RRMS and HC was a reversible two-tissue compartment model with blood volume parameter and with the dissociation rate k
4
fixed to the whole-brain value. Exploratory group level comparisons demonstrated an increased volume of distribution (V
T
) and binding potential (BP
ND
) in RRMS compared with HC in normal appearing brain regions. BP
ND
in MS lesions was decreased compared with non-lesional white matter, and a further decrease was observed in gadolinium-enhancing lesions. In contrast, increased V
T
was observed in enhancing lesions, possibly resulting from disruption of the blood-brain barrier in active MS lesions. In addition, there was a high correlation between parameters obtained from 60- to 90-min datasets, although analyses using 60-min data led to a slight underestimation in regional V
T
and BP
ND
values.
Conclusions
This first in-man study demonstrated that uptake of [
11
C]SMW139 can be quantified with PET using BP
ND
as a measure for specific binding in healthy controls and RRMS patients. Additional studies are warranted for further clinical evaluation of this novel neuroinflammation tracer.</description><subject>Binding</subject><subject>Blood volume</subject><subject>Blood-brain barrier</subject><subject>Cardiology</subject><subject>Disruption</subject><subject>Evaluation</subject><subject>Gadolinium</subject><subject>Imaging</subject><subject>In vivo methods and tests</subject><subject>Inflammation</subject><subject>Lesions</subject><subject>Mathematical models</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolites</subject><subject>Microglia</subject><subject>Multiple sclerosis</subject><subject>Neurology</subject><subject>Nuclear Medicine</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Parameters</subject><subject>Pharmacokinetics</subject><subject>Positron emission</subject><subject>Positron emission tomography</subject><subject>Radiology</subject><subject>Substantia alba</subject><subject>Tissues</subject><subject>Tomography</subject><issn>1619-7070</issn><issn>1619-7089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp9UdFKHDEUDaK41voDPgX6PHozSSYTHwqytFqwKGhpoZSQnbnjZp2ZrMnMsvr1jbti6YsPl9xwzzn3Hg4hxwxOGIA6jQC51BmwVEJKyNY75IAV6aug1LtvvYIJ-RDjAoCVean3yYQzBZIpcUCe7-ZIb_JfigascDn4QIdgKwz0N2PTP7fffzKuqY3U9tT1dOVWnnY2PCSAb2iPY_Cub1rbdXZwfoPpxnZwyxZprFoMPrp4Ri1tXIhD9jJOSnEY66ePZK-xbcSj1_eQ_Pj65W56mV1dX3ybnl9lleD5OiukKi1XAA2THLnNS461rqoaCzFruK6bQulCANaltRK11qgll1iwHEomZ_yQfN7qLsdZh3WFfXLYmmVwyciT8daZ_ye9m5t7vzKFVkKCTgKfXgWCfxwxDmbhx9Cnm03O042iFEIkVL5FVclzDNi8bWBgXvIy27xMysts8jLrROJbUkzg_h7DP-l3WH8B5DOYDg</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Hagens, Marloes H. J.</creator><creator>Golla, Sandeep S. V.</creator><creator>Janssen, Bieneke</creator><creator>Vugts, Danielle J.</creator><creator>Beaino, Wissam</creator><creator>Windhorst, Albert D.</creator><creator>O’Brien-Brown, James</creator><creator>Kassiou, Michael</creator><creator>Schuit, Robert C.</creator><creator>Schwarte, Lothar A.</creator><creator>de Vries, Helga E.</creator><creator>Killestein, Joep</creator><creator>Barkhof, Frederik</creator><creator>van Berckel, Bart N. M.</creator><creator>Lammertsma, Adriaan A.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7115-6833</orcidid></search><sort><creationdate>20200201</creationdate><title>The P2X7 receptor tracer [11C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study</title><author>Hagens, Marloes H. J. ; Golla, Sandeep S. V. ; Janssen, Bieneke ; Vugts, Danielle J. ; Beaino, Wissam ; Windhorst, Albert D. ; O’Brien-Brown, James ; Kassiou, Michael ; Schuit, Robert C. ; Schwarte, Lothar A. ; de Vries, Helga E. ; Killestein, Joep ; Barkhof, Frederik ; van Berckel, Bart N. M. ; Lammertsma, Adriaan A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432x-6578a3700f153e3a283ed9ccde64bf39df679640ed8aa5e999e9535e6120815b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Binding</topic><topic>Blood volume</topic><topic>Blood-brain barrier</topic><topic>Cardiology</topic><topic>Disruption</topic><topic>Evaluation</topic><topic>Gadolinium</topic><topic>Imaging</topic><topic>In vivo methods and tests</topic><topic>Inflammation</topic><topic>Lesions</topic><topic>Mathematical models</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolites</topic><topic>Microglia</topic><topic>Multiple sclerosis</topic><topic>Neurology</topic><topic>Nuclear Medicine</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Parameters</topic><topic>Pharmacokinetics</topic><topic>Positron emission</topic><topic>Positron emission tomography</topic><topic>Radiology</topic><topic>Substantia alba</topic><topic>Tissues</topic><topic>Tomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hagens, Marloes H. J.</creatorcontrib><creatorcontrib>Golla, Sandeep S. V.</creatorcontrib><creatorcontrib>Janssen, Bieneke</creatorcontrib><creatorcontrib>Vugts, Danielle J.</creatorcontrib><creatorcontrib>Beaino, Wissam</creatorcontrib><creatorcontrib>Windhorst, Albert D.</creatorcontrib><creatorcontrib>O’Brien-Brown, James</creatorcontrib><creatorcontrib>Kassiou, Michael</creatorcontrib><creatorcontrib>Schuit, Robert C.</creatorcontrib><creatorcontrib>Schwarte, Lothar A.</creatorcontrib><creatorcontrib>de Vries, Helga E.</creatorcontrib><creatorcontrib>Killestein, Joep</creatorcontrib><creatorcontrib>Barkhof, Frederik</creatorcontrib><creatorcontrib>van Berckel, Bart N. M.</creatorcontrib><creatorcontrib>Lammertsma, Adriaan A.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Biological Science Journals</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of nuclear medicine and molecular imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hagens, Marloes H. J.</au><au>Golla, Sandeep S. V.</au><au>Janssen, Bieneke</au><au>Vugts, Danielle J.</au><au>Beaino, Wissam</au><au>Windhorst, Albert D.</au><au>O’Brien-Brown, James</au><au>Kassiou, Michael</au><au>Schuit, Robert C.</au><au>Schwarte, Lothar A.</au><au>de Vries, Helga E.</au><au>Killestein, Joep</au><au>Barkhof, Frederik</au><au>van Berckel, Bart N. M.</au><au>Lammertsma, Adriaan A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The P2X7 receptor tracer [11C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study</atitle><jtitle>European journal of nuclear medicine and molecular imaging</jtitle><stitle>Eur J Nucl Med Mol Imaging</stitle><date>2020-02-01</date><risdate>2020</risdate><volume>47</volume><issue>2</issue><spage>379</spage><epage>389</epage><pages>379-389</pages><issn>1619-7070</issn><eissn>1619-7089</eissn><abstract>Purpose
The novel PET tracer [
11
C]SMW139 binds with high affinity to the P2X
7
receptor, which is expressed on pro-inflammatory microglia. The purposes of this first in-man study were to characterise pharmacokinetics of [
11
C]SMW139 in patients with active relapsing remitting multiple sclerosis (RRMS) and healthy controls (HC) and to evaluate its potential to identify
in vivo
neuroinflammation in RRMS.
Methods
Five RRMS patients and 5 age-matched HC underwent 90-min dynamic [
11
C]SMW139 PET scans, with online continuous and manual arterial sampling to generate a metabolite-corrected arterial plasma input function. Tissue time activity curves were fitted to single- and two-tissue compartment models, and the model that provided the best fits was determined using the Akaike information criterion.
Results
The optimal model for describing [
11
C]SMW139 kinetics in both RRMS and HC was a reversible two-tissue compartment model with blood volume parameter and with the dissociation rate k
4
fixed to the whole-brain value. Exploratory group level comparisons demonstrated an increased volume of distribution (V
T
) and binding potential (BP
ND
) in RRMS compared with HC in normal appearing brain regions. BP
ND
in MS lesions was decreased compared with non-lesional white matter, and a further decrease was observed in gadolinium-enhancing lesions. In contrast, increased V
T
was observed in enhancing lesions, possibly resulting from disruption of the blood-brain barrier in active MS lesions. In addition, there was a high correlation between parameters obtained from 60- to 90-min datasets, although analyses using 60-min data led to a slight underestimation in regional V
T
and BP
ND
values.
Conclusions
This first in-man study demonstrated that uptake of [
11
C]SMW139 can be quantified with PET using BP
ND
as a measure for specific binding in healthy controls and RRMS patients. Additional studies are warranted for further clinical evaluation of this novel neuroinflammation tracer.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>31705174</pmid><doi>10.1007/s00259-019-04550-x</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-7115-6833</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 1619-7070 1619-7089 |
| language | eng |
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| source | SpringerLink Journals - AutoHoldings |
| subjects | Binding Blood volume Blood-brain barrier Cardiology Disruption Evaluation Gadolinium Imaging In vivo methods and tests Inflammation Lesions Mathematical models Medicine Medicine & Public Health Metabolites Microglia Multiple sclerosis Neurology Nuclear Medicine Oncology Original Original Article Orthopedics Parameters Pharmacokinetics Positron emission Positron emission tomography Radiology Substantia alba Tissues Tomography |
| title | The P2X7 receptor tracer [11C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study |
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