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[18F]-DPA-714 PET as a specific in vivo marker of early microglial activation in a rat model of progressive dopaminergic degeneration
Purpose To study the feasibility of the in vivo [ 18 F]-DPA-714 TSPO positron emission tomography (PET) to detect glial activation in a rat model of progressive parkinsonism induced by viral-mediated overexpression of A53T mutated human α-synuclein (hα-syn) in the substantia nigra pars compacta (SNp...
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| Published in: | European journal of nuclear medicine and molecular imaging 2020-10, Vol.47 (11), p.2602-2612 |
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| container_end_page | 2612 |
| container_issue | 11 |
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| container_title | European journal of nuclear medicine and molecular imaging |
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| creator | Rodríguez-Chinchilla, Tatiana Quiroga-Varela, Ana Molinet-Dronda, Francisco Belloso-Iguerategui, Arantzazu Merino-Galan, Leyre Jimenez-Urbieta, Haritz Gago, Belén Rodriguez-Oroz, María Cruz |
| description | Purpose
To study the feasibility of the in vivo [
18
F]-DPA-714 TSPO positron emission tomography (PET) to detect glial activation in a rat model of progressive parkinsonism induced by viral-mediated overexpression of A53T mutated human α-synuclein (hα-syn) in the substantia nigra pars compacta (SNpc).
Methods
We conducted a cross-sectional study in a model of progressive parkinsonism. Bilateral intranigral injections with 2/9 adeno-associated viral vectors encoding either hα-syn (AAV-hα-syn) or green fluorescent protein (AAV-GFP) were performed in rats (
n
= 60). In vivo [
18
F]-DPA-714 PET imaging was performed at different time points after inoculation (p.i.) of the viral vector (24 and 72 h and 1, 2, 3, and 16 weeks). Images were analyzed to compute values of binding potential (BP) in the SNpc and striatum using a volume of interest (VOI) analysis. Immunohistochemistry of markers of dopaminergic degeneration (tyrosine hydroxylase (TH)), microglia (Iba-1), and astrocytes (GFAP) was carried out. Binding potential (BP) of [
18
F]-DPA-714 PET in the in vivo PET study was correlated with post-mortem histological markers.
Results
In the SNpc of AAV-hα-syn rats, there was higher in vivo [
18
F]-DPA-714 BP (
p
|
| doi_str_mv | 10.1007/s00259-020-04772-4 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2382659724</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2382659724</sourcerecordid><originalsourceid>FETCH-LOGICAL-c347t-c329ea65dd7eedc1e93af734f6daf497b99501acd1dbd9c79fe54f3f74b89f8a3</originalsourceid><addsrcrecordid>eNp9kMtOBCEQRYnR-P4BF4alm1ag6aZZGh0fiYkudGUMqYFigvZjhJ5J_AD_W8ZRl26gEs69oQ4hR5ydcsbUWWJMVLpgghVMKiUKuUF2ec11oVijN_9mxXbIXkqvjPFGNHqb7JRCsLqRbJd8PvPm6qW4fDgvFJf0YfJIIVGgaY42-GBp6OkyLAfaQXzDSAdPEWL7Qbtg4zBrA7QU7BiWMIahX9FAI4y0Gxy2K3qeqYgphSVSN8yhCz3GWS52OMM8fucOyJaHNuHhz71Pnq4mjxc3xd399e3F-V1hS6nGfAqNUFfOKURnOeoSvCqlrx14qdVU64pxsI67qdNWaY-V9KVXctpo30C5T07WvflX7wtMo-lCsti20OOwSEaUjagrrYTMqFijec2UInozjyFL-DCcmZV-s9Zvsn7zrd-sQsc__Ytph-4v8us7A-UaSPmpn2E0r8Mi9nnn_2q_AAHMkYk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2382659724</pqid></control><display><type>article</type><title>[18F]-DPA-714 PET as a specific in vivo marker of early microglial activation in a rat model of progressive dopaminergic degeneration</title><source>Springer Nature</source><creator>Rodríguez-Chinchilla, Tatiana ; Quiroga-Varela, Ana ; Molinet-Dronda, Francisco ; Belloso-Iguerategui, Arantzazu ; Merino-Galan, Leyre ; Jimenez-Urbieta, Haritz ; Gago, Belén ; Rodriguez-Oroz, María Cruz</creator><creatorcontrib>Rodríguez-Chinchilla, Tatiana ; Quiroga-Varela, Ana ; Molinet-Dronda, Francisco ; Belloso-Iguerategui, Arantzazu ; Merino-Galan, Leyre ; Jimenez-Urbieta, Haritz ; Gago, Belén ; Rodriguez-Oroz, María Cruz</creatorcontrib><description>Purpose
To study the feasibility of the in vivo [
18
F]-DPA-714 TSPO positron emission tomography (PET) to detect glial activation in a rat model of progressive parkinsonism induced by viral-mediated overexpression of A53T mutated human α-synuclein (hα-syn) in the substantia nigra pars compacta (SNpc).
Methods
We conducted a cross-sectional study in a model of progressive parkinsonism. Bilateral intranigral injections with 2/9 adeno-associated viral vectors encoding either hα-syn (AAV-hα-syn) or green fluorescent protein (AAV-GFP) were performed in rats (
n
= 60). In vivo [
18
F]-DPA-714 PET imaging was performed at different time points after inoculation (p.i.) of the viral vector (24 and 72 h and 1, 2, 3, and 16 weeks). Images were analyzed to compute values of binding potential (BP) in the SNpc and striatum using a volume of interest (VOI) analysis. Immunohistochemistry of markers of dopaminergic degeneration (tyrosine hydroxylase (TH)), microglia (Iba-1), and astrocytes (GFAP) was carried out. Binding potential (BP) of [
18
F]-DPA-714 PET in the in vivo PET study was correlated with post-mortem histological markers.
Results
In the SNpc of AAV-hα-syn rats, there was higher in vivo [
18
F]-DPA-714 BP (
p
< 0.05) and increased number of post-mortem Iba-1
+
cells (
p
< 0.05) from second week p.i. onwards, which were highly correlated (
p
< 0.05) between each other. These findings antedated the nigral reduction of TH
+
cells that occurs since third week p.i. (
p
< 0.01). In addition, the [
18
F]-DPA-714 BP was inversely correlated (
p
< 0.05) with the TH
+
cells. In contrast, GFAP
+
cells only increased at 16 weeks p.i. and did not correlate with the in vivo results. In the striatum, no changes in the number of Iba-1
+
and GFAP
+
cells were observed, but an increment in the [
18
F]-DPA-714 BP was found at 16 weeks p.i.
Conclusions
Our study showed that in vivo PET study with [
18
F]-DPA-714 is a selective and reliable biomarker of microglial activation and could be used to study preclinical stages of Parkinson’s disease (PD) and to monitor the progression of the disease.</description><identifier>ISSN: 1619-7070</identifier><identifier>EISSN: 1619-7089</identifier><identifier>DOI: 10.1007/s00259-020-04772-4</identifier><identifier>PMID: 32206840</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Biomarkers ; Cardiology ; Cross-Sectional Studies ; Disease Models, Animal ; Imaging ; Medicine ; Medicine & Public Health ; Microglia ; Neurology ; Nuclear Medicine ; Oncology ; Original Article ; Orthopedics ; Positron-Emission Tomography ; Pyrazoles ; Pyrimidines ; Radiology ; Rats</subject><ispartof>European journal of nuclear medicine and molecular imaging, 2020-10, Vol.47 (11), p.2602-2612</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c347t-c329ea65dd7eedc1e93af734f6daf497b99501acd1dbd9c79fe54f3f74b89f8a3</citedby><cites>FETCH-LOGICAL-c347t-c329ea65dd7eedc1e93af734f6daf497b99501acd1dbd9c79fe54f3f74b89f8a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32206840$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rodríguez-Chinchilla, Tatiana</creatorcontrib><creatorcontrib>Quiroga-Varela, Ana</creatorcontrib><creatorcontrib>Molinet-Dronda, Francisco</creatorcontrib><creatorcontrib>Belloso-Iguerategui, Arantzazu</creatorcontrib><creatorcontrib>Merino-Galan, Leyre</creatorcontrib><creatorcontrib>Jimenez-Urbieta, Haritz</creatorcontrib><creatorcontrib>Gago, Belén</creatorcontrib><creatorcontrib>Rodriguez-Oroz, María Cruz</creatorcontrib><title>[18F]-DPA-714 PET as a specific in vivo marker of early microglial activation in a rat model of progressive dopaminergic degeneration</title><title>European journal of nuclear medicine and molecular imaging</title><addtitle>Eur J Nucl Med Mol Imaging</addtitle><addtitle>Eur J Nucl Med Mol Imaging</addtitle><description>Purpose
To study the feasibility of the in vivo [
18
F]-DPA-714 TSPO positron emission tomography (PET) to detect glial activation in a rat model of progressive parkinsonism induced by viral-mediated overexpression of A53T mutated human α-synuclein (hα-syn) in the substantia nigra pars compacta (SNpc).
Methods
We conducted a cross-sectional study in a model of progressive parkinsonism. Bilateral intranigral injections with 2/9 adeno-associated viral vectors encoding either hα-syn (AAV-hα-syn) or green fluorescent protein (AAV-GFP) were performed in rats (
n
= 60). In vivo [
18
F]-DPA-714 PET imaging was performed at different time points after inoculation (p.i.) of the viral vector (24 and 72 h and 1, 2, 3, and 16 weeks). Images were analyzed to compute values of binding potential (BP) in the SNpc and striatum using a volume of interest (VOI) analysis. Immunohistochemistry of markers of dopaminergic degeneration (tyrosine hydroxylase (TH)), microglia (Iba-1), and astrocytes (GFAP) was carried out. Binding potential (BP) of [
18
F]-DPA-714 PET in the in vivo PET study was correlated with post-mortem histological markers.
Results
In the SNpc of AAV-hα-syn rats, there was higher in vivo [
18
F]-DPA-714 BP (
p
< 0.05) and increased number of post-mortem Iba-1
+
cells (
p
< 0.05) from second week p.i. onwards, which were highly correlated (
p
< 0.05) between each other. These findings antedated the nigral reduction of TH
+
cells that occurs since third week p.i. (
p
< 0.01). In addition, the [
18
F]-DPA-714 BP was inversely correlated (
p
< 0.05) with the TH
+
cells. In contrast, GFAP
+
cells only increased at 16 weeks p.i. and did not correlate with the in vivo results. In the striatum, no changes in the number of Iba-1
+
and GFAP
+
cells were observed, but an increment in the [
18
F]-DPA-714 BP was found at 16 weeks p.i.
Conclusions
Our study showed that in vivo PET study with [
18
F]-DPA-714 is a selective and reliable biomarker of microglial activation and could be used to study preclinical stages of Parkinson’s disease (PD) and to monitor the progression of the disease.</description><subject>Animals</subject><subject>Biomarkers</subject><subject>Cardiology</subject><subject>Cross-Sectional Studies</subject><subject>Disease Models, Animal</subject><subject>Imaging</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Microglia</subject><subject>Neurology</subject><subject>Nuclear Medicine</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Positron-Emission Tomography</subject><subject>Pyrazoles</subject><subject>Pyrimidines</subject><subject>Radiology</subject><subject>Rats</subject><issn>1619-7070</issn><issn>1619-7089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kMtOBCEQRYnR-P4BF4alm1ag6aZZGh0fiYkudGUMqYFigvZjhJ5J_AD_W8ZRl26gEs69oQ4hR5ydcsbUWWJMVLpgghVMKiUKuUF2ec11oVijN_9mxXbIXkqvjPFGNHqb7JRCsLqRbJd8PvPm6qW4fDgvFJf0YfJIIVGgaY42-GBp6OkyLAfaQXzDSAdPEWL7Qbtg4zBrA7QU7BiWMIahX9FAI4y0Gxy2K3qeqYgphSVSN8yhCz3GWS52OMM8fucOyJaHNuHhz71Pnq4mjxc3xd399e3F-V1hS6nGfAqNUFfOKURnOeoSvCqlrx14qdVU64pxsI67qdNWaY-V9KVXctpo30C5T07WvflX7wtMo-lCsti20OOwSEaUjagrrYTMqFijec2UInozjyFL-DCcmZV-s9Zvsn7zrd-sQsc__Ytph-4v8us7A-UaSPmpn2E0r8Mi9nnn_2q_AAHMkYk</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Rodríguez-Chinchilla, Tatiana</creator><creator>Quiroga-Varela, Ana</creator><creator>Molinet-Dronda, Francisco</creator><creator>Belloso-Iguerategui, Arantzazu</creator><creator>Merino-Galan, Leyre</creator><creator>Jimenez-Urbieta, Haritz</creator><creator>Gago, Belén</creator><creator>Rodriguez-Oroz, María Cruz</creator><general>Springer Berlin Heidelberg</general><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>7X8</scope></search><sort><creationdate>20201001</creationdate><title>[18F]-DPA-714 PET as a specific in vivo marker of early microglial activation in a rat model of progressive dopaminergic degeneration</title><author>Rodríguez-Chinchilla, Tatiana ; Quiroga-Varela, Ana ; Molinet-Dronda, Francisco ; Belloso-Iguerategui, Arantzazu ; Merino-Galan, Leyre ; Jimenez-Urbieta, Haritz ; Gago, Belén ; Rodriguez-Oroz, María Cruz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c347t-c329ea65dd7eedc1e93af734f6daf497b99501acd1dbd9c79fe54f3f74b89f8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Biomarkers</topic><topic>Cardiology</topic><topic>Cross-Sectional Studies</topic><topic>Disease Models, Animal</topic><topic>Imaging</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Microglia</topic><topic>Neurology</topic><topic>Nuclear Medicine</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Positron-Emission Tomography</topic><topic>Pyrazoles</topic><topic>Pyrimidines</topic><topic>Radiology</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodríguez-Chinchilla, Tatiana</creatorcontrib><creatorcontrib>Quiroga-Varela, Ana</creatorcontrib><creatorcontrib>Molinet-Dronda, Francisco</creatorcontrib><creatorcontrib>Belloso-Iguerategui, Arantzazu</creatorcontrib><creatorcontrib>Merino-Galan, Leyre</creatorcontrib><creatorcontrib>Jimenez-Urbieta, Haritz</creatorcontrib><creatorcontrib>Gago, Belén</creatorcontrib><creatorcontrib>Rodriguez-Oroz, María Cruz</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><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>Rodríguez-Chinchilla, Tatiana</au><au>Quiroga-Varela, Ana</au><au>Molinet-Dronda, Francisco</au><au>Belloso-Iguerategui, Arantzazu</au><au>Merino-Galan, Leyre</au><au>Jimenez-Urbieta, Haritz</au><au>Gago, Belén</au><au>Rodriguez-Oroz, María Cruz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>[18F]-DPA-714 PET as a specific in vivo marker of early microglial activation in a rat model of progressive dopaminergic degeneration</atitle><jtitle>European journal of nuclear medicine and molecular imaging</jtitle><stitle>Eur J Nucl Med Mol Imaging</stitle><addtitle>Eur J Nucl Med Mol Imaging</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>47</volume><issue>11</issue><spage>2602</spage><epage>2612</epage><pages>2602-2612</pages><issn>1619-7070</issn><eissn>1619-7089</eissn><abstract>Purpose
To study the feasibility of the in vivo [
18
F]-DPA-714 TSPO positron emission tomography (PET) to detect glial activation in a rat model of progressive parkinsonism induced by viral-mediated overexpression of A53T mutated human α-synuclein (hα-syn) in the substantia nigra pars compacta (SNpc).
Methods
We conducted a cross-sectional study in a model of progressive parkinsonism. Bilateral intranigral injections with 2/9 adeno-associated viral vectors encoding either hα-syn (AAV-hα-syn) or green fluorescent protein (AAV-GFP) were performed in rats (
n
= 60). In vivo [
18
F]-DPA-714 PET imaging was performed at different time points after inoculation (p.i.) of the viral vector (24 and 72 h and 1, 2, 3, and 16 weeks). Images were analyzed to compute values of binding potential (BP) in the SNpc and striatum using a volume of interest (VOI) analysis. Immunohistochemistry of markers of dopaminergic degeneration (tyrosine hydroxylase (TH)), microglia (Iba-1), and astrocytes (GFAP) was carried out. Binding potential (BP) of [
18
F]-DPA-714 PET in the in vivo PET study was correlated with post-mortem histological markers.
Results
In the SNpc of AAV-hα-syn rats, there was higher in vivo [
18
F]-DPA-714 BP (
p
< 0.05) and increased number of post-mortem Iba-1
+
cells (
p
< 0.05) from second week p.i. onwards, which were highly correlated (
p
< 0.05) between each other. These findings antedated the nigral reduction of TH
+
cells that occurs since third week p.i. (
p
< 0.01). In addition, the [
18
F]-DPA-714 BP was inversely correlated (
p
< 0.05) with the TH
+
cells. In contrast, GFAP
+
cells only increased at 16 weeks p.i. and did not correlate with the in vivo results. In the striatum, no changes in the number of Iba-1
+
and GFAP
+
cells were observed, but an increment in the [
18
F]-DPA-714 BP was found at 16 weeks p.i.
Conclusions
Our study showed that in vivo PET study with [
18
F]-DPA-714 is a selective and reliable biomarker of microglial activation and could be used to study preclinical stages of Parkinson’s disease (PD) and to monitor the progression of the disease.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32206840</pmid><doi>10.1007/s00259-020-04772-4</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1619-7070 |
| ispartof | European journal of nuclear medicine and molecular imaging, 2020-10, Vol.47 (11), p.2602-2612 |
| issn | 1619-7070 1619-7089 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2382659724 |
| source | Springer Nature |
| subjects | Animals Biomarkers Cardiology Cross-Sectional Studies Disease Models, Animal Imaging Medicine Medicine & Public Health Microglia Neurology Nuclear Medicine Oncology Original Article Orthopedics Positron-Emission Tomography Pyrazoles Pyrimidines Radiology Rats |
| title | [18F]-DPA-714 PET as a specific in vivo marker of early microglial activation in a rat model of progressive dopaminergic degeneration |
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