CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction
The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positr...
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| creator | English, Sean J. Sastriques, Sergio E. Detering, Lisa Sultan, Deborah Luehmann, Hannah Arif, Batool Heo, Gyu Seong Zhang, Xiaohui Laforest, Richard Zheng, Jie Lin, Chieh-Yu Gropler, Robert J. Liu, Yongjian |
| description | The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (
Cu-DOTA-ECL1i).
AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of β-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of
Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer.
Biodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10; |
| doi_str_mv | 10.1161/CIRCIMAGING.119.009889 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7101060</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2377330212</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4599-9ba98c5a422d4d181d08c48a4b4754108312eb4ba07444af52b482ce81529f9f3</originalsourceid><addsrcrecordid>eNpVkVtv1DAQhSMEohf4C5UfeUkZX5LYL0hR1C6RClSr8mw5jtMYknixHar993i1bbU8zej4zPFoviy7wnCNcYk_N-22ab_Vm_b7JgniGkBwLt5k51gwkgNweHvSn2UXIfwCKCkU_H12RgkuGSvwebY2zZagexds9G5BN7MNwabmwc3u0avduEeD8yiOBtUhmBBms0TkBlR3vZvtoiZUOx-tRvViVr8PM2qXYVLzrOIhRy092q67uHqD7r3prT7IH7J3g5qC-fhcL7OftzcPzdf87sembeq7XLNCiFx0SnBdKEZIz3rMcQ9cM65Yx6qCYeAUE9OxTkHFGFNDQTrGiTYcF0QMYqCX2Zdj7m7tZtPrtLtXk9x5Oyu_l05Z-f_LYkf56P7KCgOGElLAp-cA7_6sJkSZDqTNNKnFuDVIQquKUiCYJGt5tGrvQvBmeP0GgzwwkyfMkiDkkVkavDpd8nXsBVIysKPhyU3R-PB7Wp-Ml6NRUxwlYEorJnhOgABQAEjIUzT9B1UjpQg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2377330212</pqid></control><display><type>article</type><title>CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction</title><source>MEDLINE</source><source>American Heart Association Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>English, Sean J. ; Sastriques, Sergio E. ; Detering, Lisa ; Sultan, Deborah ; Luehmann, Hannah ; Arif, Batool ; Heo, Gyu Seong ; Zhang, Xiaohui ; Laforest, Richard ; Zheng, Jie ; Lin, Chieh-Yu ; Gropler, Robert J. ; Liu, Yongjian</creator><creatorcontrib>English, Sean J. ; Sastriques, Sergio E. ; Detering, Lisa ; Sultan, Deborah ; Luehmann, Hannah ; Arif, Batool ; Heo, Gyu Seong ; Zhang, Xiaohui ; Laforest, Richard ; Zheng, Jie ; Lin, Chieh-Yu ; Gropler, Robert J. ; Liu, Yongjian</creatorcontrib><description>The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (
Cu-DOTA-ECL1i).
AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of β-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of
Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer.
Biodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10;
<0.01). At 14 days post-AAA induction, radiotracer uptake by either group did not significantly change (AAA SUV=0.86±0.17 and sham-control SUV=0.46±0.10), independent of variations in aortic diameter. Competitive CCR2 receptor blocking significantly decreased AAA uptake (SUV=0.42±0.09). Tracer uptake in AAAs that subsequently ruptured (SUV=1.31±0.14;
<0.005) demonstrated uptake nearly twice that of nonruptured AAAs (SUV=0.73±0.11). Histopathologic characterization of rat and human AAA tissues obtained from surgery revealed increased expression of CCR2 that was co-localized with CD68
macrophages. Ex vivo autoradiography demonstrated specific binding of
Cu-DOTA-ECL1i to CCR2 in both rat and human aortic tissues.
CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.</description><identifier>ISSN: 1942-0080</identifier><identifier>ISSN: 1941-9651</identifier><identifier>EISSN: 1942-0080</identifier><identifier>DOI: 10.1161/CIRCIMAGING.119.009889</identifier><identifier>PMID: 32164451</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Aneurysm, Ruptured - diagnosis ; Aneurysm, Ruptured - genetics ; Aneurysm, Ruptured - metabolism ; Animals ; Aorta, Abdominal - diagnostic imaging ; Aorta, Abdominal - metabolism ; Aortic Aneurysm, Abdominal - diagnosis ; Aortic Aneurysm, Abdominal - genetics ; Aortic Aneurysm, Abdominal - metabolism ; Biomarkers - metabolism ; Fluorodeoxyglucose F18 - pharmacology ; Gene Expression Regulation ; Male ; Positron-Emission Tomography - methods ; Prognosis ; Radiopharmaceuticals - pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, CCR2 - biosynthesis ; Receptors, CCR2 - genetics ; RNA - genetics</subject><ispartof>Circulation. Cardiovascular imaging, 2020-03, Vol.13 (3), p.e009889-e009889</ispartof><rights>American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4599-9ba98c5a422d4d181d08c48a4b4754108312eb4ba07444af52b482ce81529f9f3</citedby><cites>FETCH-LOGICAL-c4599-9ba98c5a422d4d181d08c48a4b4754108312eb4ba07444af52b482ce81529f9f3</cites><orcidid>0000-0002-1118-1535</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3687,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32164451$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>English, Sean J.</creatorcontrib><creatorcontrib>Sastriques, Sergio E.</creatorcontrib><creatorcontrib>Detering, Lisa</creatorcontrib><creatorcontrib>Sultan, Deborah</creatorcontrib><creatorcontrib>Luehmann, Hannah</creatorcontrib><creatorcontrib>Arif, Batool</creatorcontrib><creatorcontrib>Heo, Gyu Seong</creatorcontrib><creatorcontrib>Zhang, Xiaohui</creatorcontrib><creatorcontrib>Laforest, Richard</creatorcontrib><creatorcontrib>Zheng, Jie</creatorcontrib><creatorcontrib>Lin, Chieh-Yu</creatorcontrib><creatorcontrib>Gropler, Robert J.</creatorcontrib><creatorcontrib>Liu, Yongjian</creatorcontrib><title>CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction</title><title>Circulation. Cardiovascular imaging</title><addtitle>Circ Cardiovasc Imaging</addtitle><description>The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (
Cu-DOTA-ECL1i).
AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of β-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of
Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer.
Biodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10;
<0.01). At 14 days post-AAA induction, radiotracer uptake by either group did not significantly change (AAA SUV=0.86±0.17 and sham-control SUV=0.46±0.10), independent of variations in aortic diameter. Competitive CCR2 receptor blocking significantly decreased AAA uptake (SUV=0.42±0.09). Tracer uptake in AAAs that subsequently ruptured (SUV=1.31±0.14;
<0.005) demonstrated uptake nearly twice that of nonruptured AAAs (SUV=0.73±0.11). Histopathologic characterization of rat and human AAA tissues obtained from surgery revealed increased expression of CCR2 that was co-localized with CD68
macrophages. Ex vivo autoradiography demonstrated specific binding of
Cu-DOTA-ECL1i to CCR2 in both rat and human aortic tissues.
CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.</description><subject>Aneurysm, Ruptured - diagnosis</subject><subject>Aneurysm, Ruptured - genetics</subject><subject>Aneurysm, Ruptured - metabolism</subject><subject>Animals</subject><subject>Aorta, Abdominal - diagnostic imaging</subject><subject>Aorta, Abdominal - metabolism</subject><subject>Aortic Aneurysm, Abdominal - diagnosis</subject><subject>Aortic Aneurysm, Abdominal - genetics</subject><subject>Aortic Aneurysm, Abdominal - metabolism</subject><subject>Biomarkers - metabolism</subject><subject>Fluorodeoxyglucose F18 - pharmacology</subject><subject>Gene Expression Regulation</subject><subject>Male</subject><subject>Positron-Emission Tomography - methods</subject><subject>Prognosis</subject><subject>Radiopharmaceuticals - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, CCR2 - biosynthesis</subject><subject>Receptors, CCR2 - genetics</subject><subject>RNA - genetics</subject><issn>1942-0080</issn><issn>1941-9651</issn><issn>1942-0080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkVtv1DAQhSMEohf4C5UfeUkZX5LYL0hR1C6RClSr8mw5jtMYknixHar993i1bbU8zej4zPFoviy7wnCNcYk_N-22ab_Vm_b7JgniGkBwLt5k51gwkgNweHvSn2UXIfwCKCkU_H12RgkuGSvwebY2zZagexds9G5BN7MNwabmwc3u0avduEeD8yiOBtUhmBBms0TkBlR3vZvtoiZUOx-tRvViVr8PM2qXYVLzrOIhRy092q67uHqD7r3prT7IH7J3g5qC-fhcL7OftzcPzdf87sembeq7XLNCiFx0SnBdKEZIz3rMcQ9cM65Yx6qCYeAUE9OxTkHFGFNDQTrGiTYcF0QMYqCX2Zdj7m7tZtPrtLtXk9x5Oyu_l05Z-f_LYkf56P7KCgOGElLAp-cA7_6sJkSZDqTNNKnFuDVIQquKUiCYJGt5tGrvQvBmeP0GgzwwkyfMkiDkkVkavDpd8nXsBVIysKPhyU3R-PB7Wp-Ml6NRUxwlYEorJnhOgABQAEjIUzT9B1UjpQg</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>English, Sean J.</creator><creator>Sastriques, Sergio E.</creator><creator>Detering, Lisa</creator><creator>Sultan, Deborah</creator><creator>Luehmann, Hannah</creator><creator>Arif, Batool</creator><creator>Heo, Gyu Seong</creator><creator>Zhang, Xiaohui</creator><creator>Laforest, Richard</creator><creator>Zheng, Jie</creator><creator>Lin, Chieh-Yu</creator><creator>Gropler, Robert J.</creator><creator>Liu, Yongjian</creator><general>American Heart Association, Inc</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><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1118-1535</orcidid></search><sort><creationdate>20200301</creationdate><title>CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction</title><author>English, Sean J. ; Sastriques, Sergio E. ; Detering, Lisa ; Sultan, Deborah ; Luehmann, Hannah ; Arif, Batool ; Heo, Gyu Seong ; Zhang, Xiaohui ; Laforest, Richard ; Zheng, Jie ; Lin, Chieh-Yu ; Gropler, Robert J. ; Liu, Yongjian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4599-9ba98c5a422d4d181d08c48a4b4754108312eb4ba07444af52b482ce81529f9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aneurysm, Ruptured - diagnosis</topic><topic>Aneurysm, Ruptured - genetics</topic><topic>Aneurysm, Ruptured - metabolism</topic><topic>Animals</topic><topic>Aorta, Abdominal - diagnostic imaging</topic><topic>Aorta, Abdominal - metabolism</topic><topic>Aortic Aneurysm, Abdominal - diagnosis</topic><topic>Aortic Aneurysm, Abdominal - genetics</topic><topic>Aortic Aneurysm, Abdominal - metabolism</topic><topic>Biomarkers - metabolism</topic><topic>Fluorodeoxyglucose F18 - pharmacology</topic><topic>Gene Expression Regulation</topic><topic>Male</topic><topic>Positron-Emission Tomography - methods</topic><topic>Prognosis</topic><topic>Radiopharmaceuticals - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, CCR2 - biosynthesis</topic><topic>Receptors, CCR2 - genetics</topic><topic>RNA - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>English, Sean J.</creatorcontrib><creatorcontrib>Sastriques, Sergio E.</creatorcontrib><creatorcontrib>Detering, Lisa</creatorcontrib><creatorcontrib>Sultan, Deborah</creatorcontrib><creatorcontrib>Luehmann, Hannah</creatorcontrib><creatorcontrib>Arif, Batool</creatorcontrib><creatorcontrib>Heo, Gyu Seong</creatorcontrib><creatorcontrib>Zhang, Xiaohui</creatorcontrib><creatorcontrib>Laforest, Richard</creatorcontrib><creatorcontrib>Zheng, Jie</creatorcontrib><creatorcontrib>Lin, Chieh-Yu</creatorcontrib><creatorcontrib>Gropler, Robert J.</creatorcontrib><creatorcontrib>Liu, Yongjian</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Circulation. Cardiovascular imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>English, Sean J.</au><au>Sastriques, Sergio E.</au><au>Detering, Lisa</au><au>Sultan, Deborah</au><au>Luehmann, Hannah</au><au>Arif, Batool</au><au>Heo, Gyu Seong</au><au>Zhang, Xiaohui</au><au>Laforest, Richard</au><au>Zheng, Jie</au><au>Lin, Chieh-Yu</au><au>Gropler, Robert J.</au><au>Liu, Yongjian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction</atitle><jtitle>Circulation. Cardiovascular imaging</jtitle><addtitle>Circ Cardiovasc Imaging</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>13</volume><issue>3</issue><spage>e009889</spage><epage>e009889</epage><pages>e009889-e009889</pages><issn>1942-0080</issn><issn>1941-9651</issn><eissn>1942-0080</eissn><abstract>The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (
Cu-DOTA-ECL1i).
AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of β-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of
Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer.
Biodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10;
<0.01). At 14 days post-AAA induction, radiotracer uptake by either group did not significantly change (AAA SUV=0.86±0.17 and sham-control SUV=0.46±0.10), independent of variations in aortic diameter. Competitive CCR2 receptor blocking significantly decreased AAA uptake (SUV=0.42±0.09). Tracer uptake in AAAs that subsequently ruptured (SUV=1.31±0.14;
<0.005) demonstrated uptake nearly twice that of nonruptured AAAs (SUV=0.73±0.11). Histopathologic characterization of rat and human AAA tissues obtained from surgery revealed increased expression of CCR2 that was co-localized with CD68
macrophages. Ex vivo autoradiography demonstrated specific binding of
Cu-DOTA-ECL1i to CCR2 in both rat and human aortic tissues.
CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>32164451</pmid><doi>10.1161/CIRCIMAGING.119.009889</doi><orcidid>https://orcid.org/0000-0002-1118-1535</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 1942-0080 1941-9651 1942-0080 |
| language | eng |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Aneurysm, Ruptured - diagnosis Aneurysm, Ruptured - genetics Aneurysm, Ruptured - metabolism Animals Aorta, Abdominal - diagnostic imaging Aorta, Abdominal - metabolism Aortic Aneurysm, Abdominal - diagnosis Aortic Aneurysm, Abdominal - genetics Aortic Aneurysm, Abdominal - metabolism Biomarkers - metabolism Fluorodeoxyglucose F18 - pharmacology Gene Expression Regulation Male Positron-Emission Tomography - methods Prognosis Radiopharmaceuticals - pharmacology Rats Rats, Sprague-Dawley Receptors, CCR2 - biosynthesis Receptors, CCR2 - genetics RNA - genetics |
| title | CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction |
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