Positron emission tomography/computed tomographic and magnetic resonance imaging in a murine model of progressive atherosclerosis using (64)Cu-labeled glycoprotein VI-Fc
Plaque erosion leads to exposure of subendothelial collagen, which may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion using (64)Cu-labeled GPVI-Fc (fragment crystallized). Four-week-old male apolipoprotein E-deficient (ApoE(-/-)) mice (n=6) were fed a high-fat diet for 12 w...
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| Veröffentlicht in: | Circulation. Cardiovascular imaging 2013-11, Vol.6 (6), p.957-964 |
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| creator | Bigalke, Boris Phinikaridou, Alkystis Andia, Marcelo E Cooper, Margaret S Schuster, Andreas Schönberger, Tanja Griessinger, Christoph M Wurster, Thomas Onthank, David Ungerer, Martin Gawaz, Meinrad Nagel, Eike Botnar, Rene M |
| description | Plaque erosion leads to exposure of subendothelial collagen, which may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion using (64)Cu-labeled GPVI-Fc (fragment crystallized).
Four-week-old male apolipoprotein E-deficient (ApoE(-/-)) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wild-type (WT) mice served as controls (n=6). Another group of WT mice received a ligation injury of the left carotid artery (n=6) or sham procedure (n=4). All mice received a total activity of ≈12 MBq (64)Cu-GPVI-Fc by tail vein injection followed by delayed (24 hours) positron emission tomography using a NanoPET/computed tomographic scanner (Mediso, Hungary; Bioscan, USA) with an acquisition time of 1800 seconds. Seventy-two hours after positron emission tomography/computed tomography, all mice were scanned 2 hours after intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-specific MR contrast agent. MRI was performed on a 3-T clinical scanner (Philips Healthcare, Best, The Netherlands). In ApoE(-/-) mice, the (64)Cu-GPVI-Fc uptake in the aortic arch was significantly higher compared with WT mice (ApoE(-/-): 13.2±1.5 Bq/cm(3) versus WT mice: 5.1±0.5 Bq/cm(3); P=0.028). (64)Cu-GPVI-Fc uptake was also higher in the injured left carotid artery wall compared with the intact right carotid artery of WT mice and as a trend compared with sham procedure (injured: 20.7±1.3 Bq/cm(3) versus intact: 2.3±0.5 Bq/cm(3); P=0.028 versus sham: 12.7±1.7 Bq/cm(3); P=0.068). Results were confirmed by ex vivo histology and in vivo MRI with elastin-specific MR contrast agent that measures plaque burden and vessel wall remodeling. Higher R1 relaxation rates were found in the injured carotid wall with a T1 mapping sequence (injured: 1.44±0.08 s(-1) versus intact: 0.91±0.02 s(-1); P=0.028 versus sham: 0.97±0.05 s(-1); P=0.068) and in the aortic arch of ApoE(-/-) mice compared with WT mice (ApoE(-/-): 1.49±0.05 s(-1) versus WT: 0.92±0.04 s(-1); P=0.028).
(64)Cu-GPVI-Fc positron emission tomographic imaging allows identification of exposed subendothelial collagen in injured WT and high-fat diet-fed ApoE(-/-) mice. |
| doi_str_mv | 10.1161/CIRCIMAGING.113.000488 |
| format | Article |
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Four-week-old male apolipoprotein E-deficient (ApoE(-/-)) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wild-type (WT) mice served as controls (n=6). Another group of WT mice received a ligation injury of the left carotid artery (n=6) or sham procedure (n=4). All mice received a total activity of ≈12 MBq (64)Cu-GPVI-Fc by tail vein injection followed by delayed (24 hours) positron emission tomography using a NanoPET/computed tomographic scanner (Mediso, Hungary; Bioscan, USA) with an acquisition time of 1800 seconds. Seventy-two hours after positron emission tomography/computed tomography, all mice were scanned 2 hours after intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-specific MR contrast agent. MRI was performed on a 3-T clinical scanner (Philips Healthcare, Best, The Netherlands). In ApoE(-/-) mice, the (64)Cu-GPVI-Fc uptake in the aortic arch was significantly higher compared with WT mice (ApoE(-/-): 13.2±1.5 Bq/cm(3) versus WT mice: 5.1±0.5 Bq/cm(3); P=0.028). (64)Cu-GPVI-Fc uptake was also higher in the injured left carotid artery wall compared with the intact right carotid artery of WT mice and as a trend compared with sham procedure (injured: 20.7±1.3 Bq/cm(3) versus intact: 2.3±0.5 Bq/cm(3); P=0.028 versus sham: 12.7±1.7 Bq/cm(3); P=0.068). Results were confirmed by ex vivo histology and in vivo MRI with elastin-specific MR contrast agent that measures plaque burden and vessel wall remodeling. Higher R1 relaxation rates were found in the injured carotid wall with a T1 mapping sequence (injured: 1.44±0.08 s(-1) versus intact: 0.91±0.02 s(-1); P=0.028 versus sham: 0.97±0.05 s(-1); P=0.068) and in the aortic arch of ApoE(-/-) mice compared with WT mice (ApoE(-/-): 1.49±0.05 s(-1) versus WT: 0.92±0.04 s(-1); P=0.028).
(64)Cu-GPVI-Fc positron emission tomographic imaging allows identification of exposed subendothelial collagen in injured WT and high-fat diet-fed ApoE(-/-) mice.</description><identifier>EISSN: 1942-0080</identifier><identifier>DOI: 10.1161/CIRCIMAGING.113.000488</identifier><identifier>PMID: 24107491</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Atherosclerosis - diagnosis ; Carotid Artery, Common ; Copper Radioisotopes ; Disease Models, Animal ; Magnetic Resonance Imaging - methods ; Male ; Mice ; Mice, Inbred C57BL ; Platelet Membrane Glycoproteins ; Positron-Emission Tomography - methods ; Reproducibility of Results ; Tomography, X-Ray Computed - methods</subject><ispartof>Circulation. Cardiovascular imaging, 2013-11, Vol.6 (6), p.957-964</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24107491$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bigalke, Boris</creatorcontrib><creatorcontrib>Phinikaridou, Alkystis</creatorcontrib><creatorcontrib>Andia, Marcelo E</creatorcontrib><creatorcontrib>Cooper, Margaret S</creatorcontrib><creatorcontrib>Schuster, Andreas</creatorcontrib><creatorcontrib>Schönberger, Tanja</creatorcontrib><creatorcontrib>Griessinger, Christoph M</creatorcontrib><creatorcontrib>Wurster, Thomas</creatorcontrib><creatorcontrib>Onthank, David</creatorcontrib><creatorcontrib>Ungerer, Martin</creatorcontrib><creatorcontrib>Gawaz, Meinrad</creatorcontrib><creatorcontrib>Nagel, Eike</creatorcontrib><creatorcontrib>Botnar, Rene M</creatorcontrib><title>Positron emission tomography/computed tomographic and magnetic resonance imaging in a murine model of progressive atherosclerosis using (64)Cu-labeled glycoprotein VI-Fc</title><title>Circulation. Cardiovascular imaging</title><addtitle>Circ Cardiovasc Imaging</addtitle><description>Plaque erosion leads to exposure of subendothelial collagen, which may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion using (64)Cu-labeled GPVI-Fc (fragment crystallized).
Four-week-old male apolipoprotein E-deficient (ApoE(-/-)) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wild-type (WT) mice served as controls (n=6). Another group of WT mice received a ligation injury of the left carotid artery (n=6) or sham procedure (n=4). All mice received a total activity of ≈12 MBq (64)Cu-GPVI-Fc by tail vein injection followed by delayed (24 hours) positron emission tomography using a NanoPET/computed tomographic scanner (Mediso, Hungary; Bioscan, USA) with an acquisition time of 1800 seconds. Seventy-two hours after positron emission tomography/computed tomography, all mice were scanned 2 hours after intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-specific MR contrast agent. MRI was performed on a 3-T clinical scanner (Philips Healthcare, Best, The Netherlands). In ApoE(-/-) mice, the (64)Cu-GPVI-Fc uptake in the aortic arch was significantly higher compared with WT mice (ApoE(-/-): 13.2±1.5 Bq/cm(3) versus WT mice: 5.1±0.5 Bq/cm(3); P=0.028). (64)Cu-GPVI-Fc uptake was also higher in the injured left carotid artery wall compared with the intact right carotid artery of WT mice and as a trend compared with sham procedure (injured: 20.7±1.3 Bq/cm(3) versus intact: 2.3±0.5 Bq/cm(3); P=0.028 versus sham: 12.7±1.7 Bq/cm(3); P=0.068). Results were confirmed by ex vivo histology and in vivo MRI with elastin-specific MR contrast agent that measures plaque burden and vessel wall remodeling. Higher R1 relaxation rates were found in the injured carotid wall with a T1 mapping sequence (injured: 1.44±0.08 s(-1) versus intact: 0.91±0.02 s(-1); P=0.028 versus sham: 0.97±0.05 s(-1); P=0.068) and in the aortic arch of ApoE(-/-) mice compared with WT mice (ApoE(-/-): 1.49±0.05 s(-1) versus WT: 0.92±0.04 s(-1); P=0.028).
(64)Cu-GPVI-Fc positron emission tomographic imaging allows identification of exposed subendothelial collagen in injured WT and high-fat diet-fed ApoE(-/-) mice.</description><subject>Animals</subject><subject>Atherosclerosis - diagnosis</subject><subject>Carotid Artery, Common</subject><subject>Copper Radioisotopes</subject><subject>Disease Models, Animal</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Platelet Membrane Glycoproteins</subject><subject>Positron-Emission Tomography - methods</subject><subject>Reproducibility of Results</subject><subject>Tomography, X-Ray Computed - methods</subject><issn>1942-0080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUMtKxDAUDYI4vn5BstRFx9w2bdOlFB0L4wNRtyWT3NZIm9SmFeaT_EszqLi5j8N5wCHkDNgSIIPLsnoqq7urVXW_CkCyZIxxIfbIIRQ8jhgTbEGOvH9nLEtYKg7IIubAcl7AIfl6dN5Mo7MUe-O9CcfketeOcnjbXirXD_OE-h8zikqraS9bi1N4RvTOSquQmoAZ21JjqaT9PBqLtHcaO-oaOoxBjsH_E6mc3nB0XnW7aTyd_U52nvGLco46ucEuBLbdVrmgmjD4vVbRjToh-43sPJ7-7mPycnP9XN5G64dVVV6towHibIogBWRFIXLMIU6bTOlYyiZXkKpCFEJokUKxAYUyAZ3kTELDNTSx4pnKdSGSY3L-4xvSP2b0Ux2KUdh10qKbfQ08g4RDLOJAPfulzpsedT2MoYRxW__Vm3wDYwyAcA</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Bigalke, Boris</creator><creator>Phinikaridou, Alkystis</creator><creator>Andia, Marcelo E</creator><creator>Cooper, Margaret S</creator><creator>Schuster, Andreas</creator><creator>Schönberger, Tanja</creator><creator>Griessinger, Christoph M</creator><creator>Wurster, Thomas</creator><creator>Onthank, David</creator><creator>Ungerer, Martin</creator><creator>Gawaz, Meinrad</creator><creator>Nagel, Eike</creator><creator>Botnar, Rene M</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201311</creationdate><title>Positron emission tomography/computed tomographic and magnetic resonance imaging in a murine model of progressive atherosclerosis using (64)Cu-labeled glycoprotein VI-Fc</title><author>Bigalke, Boris ; Phinikaridou, Alkystis ; Andia, Marcelo E ; Cooper, Margaret S ; Schuster, Andreas ; Schönberger, Tanja ; Griessinger, Christoph M ; Wurster, Thomas ; Onthank, David ; Ungerer, Martin ; Gawaz, Meinrad ; Nagel, Eike ; Botnar, Rene M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p126t-151e09987e7125f6cd2aaf7c15c98988d8519b1cea31d370a1f4d1f2c46c7d983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Atherosclerosis - diagnosis</topic><topic>Carotid Artery, Common</topic><topic>Copper Radioisotopes</topic><topic>Disease Models, Animal</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Platelet Membrane Glycoproteins</topic><topic>Positron-Emission Tomography - methods</topic><topic>Reproducibility of Results</topic><topic>Tomography, X-Ray Computed - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bigalke, Boris</creatorcontrib><creatorcontrib>Phinikaridou, Alkystis</creatorcontrib><creatorcontrib>Andia, Marcelo E</creatorcontrib><creatorcontrib>Cooper, Margaret S</creatorcontrib><creatorcontrib>Schuster, Andreas</creatorcontrib><creatorcontrib>Schönberger, Tanja</creatorcontrib><creatorcontrib>Griessinger, Christoph M</creatorcontrib><creatorcontrib>Wurster, Thomas</creatorcontrib><creatorcontrib>Onthank, David</creatorcontrib><creatorcontrib>Ungerer, Martin</creatorcontrib><creatorcontrib>Gawaz, Meinrad</creatorcontrib><creatorcontrib>Nagel, Eike</creatorcontrib><creatorcontrib>Botnar, Rene M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation. Cardiovascular imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bigalke, Boris</au><au>Phinikaridou, Alkystis</au><au>Andia, Marcelo E</au><au>Cooper, Margaret S</au><au>Schuster, Andreas</au><au>Schönberger, Tanja</au><au>Griessinger, Christoph M</au><au>Wurster, Thomas</au><au>Onthank, David</au><au>Ungerer, Martin</au><au>Gawaz, Meinrad</au><au>Nagel, Eike</au><au>Botnar, Rene M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Positron emission tomography/computed tomographic and magnetic resonance imaging in a murine model of progressive atherosclerosis using (64)Cu-labeled glycoprotein VI-Fc</atitle><jtitle>Circulation. Cardiovascular imaging</jtitle><addtitle>Circ Cardiovasc Imaging</addtitle><date>2013-11</date><risdate>2013</risdate><volume>6</volume><issue>6</issue><spage>957</spage><epage>964</epage><pages>957-964</pages><eissn>1942-0080</eissn><abstract>Plaque erosion leads to exposure of subendothelial collagen, which may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion using (64)Cu-labeled GPVI-Fc (fragment crystallized).
Four-week-old male apolipoprotein E-deficient (ApoE(-/-)) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wild-type (WT) mice served as controls (n=6). Another group of WT mice received a ligation injury of the left carotid artery (n=6) or sham procedure (n=4). All mice received a total activity of ≈12 MBq (64)Cu-GPVI-Fc by tail vein injection followed by delayed (24 hours) positron emission tomography using a NanoPET/computed tomographic scanner (Mediso, Hungary; Bioscan, USA) with an acquisition time of 1800 seconds. Seventy-two hours after positron emission tomography/computed tomography, all mice were scanned 2 hours after intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-specific MR contrast agent. MRI was performed on a 3-T clinical scanner (Philips Healthcare, Best, The Netherlands). In ApoE(-/-) mice, the (64)Cu-GPVI-Fc uptake in the aortic arch was significantly higher compared with WT mice (ApoE(-/-): 13.2±1.5 Bq/cm(3) versus WT mice: 5.1±0.5 Bq/cm(3); P=0.028). (64)Cu-GPVI-Fc uptake was also higher in the injured left carotid artery wall compared with the intact right carotid artery of WT mice and as a trend compared with sham procedure (injured: 20.7±1.3 Bq/cm(3) versus intact: 2.3±0.5 Bq/cm(3); P=0.028 versus sham: 12.7±1.7 Bq/cm(3); P=0.068). Results were confirmed by ex vivo histology and in vivo MRI with elastin-specific MR contrast agent that measures plaque burden and vessel wall remodeling. Higher R1 relaxation rates were found in the injured carotid wall with a T1 mapping sequence (injured: 1.44±0.08 s(-1) versus intact: 0.91±0.02 s(-1); P=0.028 versus sham: 0.97±0.05 s(-1); P=0.068) and in the aortic arch of ApoE(-/-) mice compared with WT mice (ApoE(-/-): 1.49±0.05 s(-1) versus WT: 0.92±0.04 s(-1); P=0.028).
(64)Cu-GPVI-Fc positron emission tomographic imaging allows identification of exposed subendothelial collagen in injured WT and high-fat diet-fed ApoE(-/-) mice.</abstract><cop>United States</cop><pmid>24107491</pmid><doi>10.1161/CIRCIMAGING.113.000488</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Atherosclerosis - diagnosis Carotid Artery, Common Copper Radioisotopes Disease Models, Animal Magnetic Resonance Imaging - methods Male Mice Mice, Inbred C57BL Platelet Membrane Glycoproteins Positron-Emission Tomography - methods Reproducibility of Results Tomography, X-Ray Computed - methods |
| title | Positron emission tomography/computed tomographic and magnetic resonance imaging in a murine model of progressive atherosclerosis using (64)Cu-labeled glycoprotein VI-Fc |
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