Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression
Purpose Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis....
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| Veröffentlicht in: | Molecular imaging and biology 2017-08, Vol.19 (4), p.531-539 |
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| creator | Shimizu, Yoichi Hanzawa, Hiroko Zhao, Yan Fukura, Sagiri Nishijima, Ken-ichi Sakamoto, Takeshi Zhao, Songji Tamaki, Nagara Ogawa, Mikako Kuge, Yuji |
| description | Purpose
Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis. However, IgG accumulates nonspecifically in atherosclerotic regions, and its accumulation mechanisms have not yet been clarified in detail. Therefore, we explored IgG accumulation mechanisms in atherosclerotic lesions and examined images of radiolabeled IgG for the diagnosis of atherosclerosis.
Procedures
Mouse IgG without specificity to biomolecules was labeled with technetium-99m via 6-hydrazinonicotinate to yield [
99m
Tc]IgG. ApoE
−/−
or C57BL/6J mice were injected intravenously with [
99m
Tc]IgG, and their aortas were excised 24 h after injection. After radioactivity measurement, serial aortic sections were autoradiographically and histopathologically examined. RAW264.7 macrophages were polarized into M1 or M2 and then treated with [
99m
Tc]IgG. The radioactivities in the cells were measured after 1 h of incubation. [
99m
Tc]IgG uptake in M1 macrophages was also evaluated after the pretreatment with an anti-Fcγ receptor (FcγR) antibody. The expression levels of FcγRs in the cells were measured by western blot analysis.
Results
[
99m
Tc]IgG accumulation levels in the aortas were significantly higher in apoE
−/−
mice than in C57BL/6J mice (5.1 ± 1.4 vs 2.8 ± 0.5 %ID/g,
p
|
| doi_str_mv | 10.1007/s11307-016-1036-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1852688999</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1852688999</sourcerecordid><originalsourceid>FETCH-LOGICAL-c525t-71023f405ca79ef8826d7cc108626b28d7bffa2bfe4e7bb5101437e96e9f486d3</originalsourceid><addsrcrecordid>eNp1kcFu1DAQhiMEoqXwAFyQJS7lEPA4ie0cl6oskbqih3K2HGecpnLsYCcSPApvi1dbEELiMrY83__PyH9RvAb6HigVHxJARUVJgZdAK17KJ8U5SE5LRil7mu9NfgResbPiRUoPlIIAVj0vzphoJdSCnhc_u3nefBhd6Dc3ebInl924f1d-1AkH0s16nPxIbmPokeyM2ebN6RUTyegByEGbGJZ7PWLZeTu5NebmQHbrPcaQjMt1nQy5dfrblkWdH3DBXPxKgiV5ELnTccSVHIJDszkk19-XiClNwb8snlntEr56PC-Kr5-u764-lzdf9t3V7qY0DWvWUgBlla1pY7Ro0UrJ-CCMASo54z2Tg-it1ay3WKPo-wYo1JXAlmNra8mH6qK4PPkuMRy3XNU8JYPOaY9hSwpkw7iUbdtm9O0_6EPYos_bKWiBAxUtE5mCE5X_JqWIVi1xmnX8oYCqY27qlJvKualjbkpmzZtH562fcfij-B1UBtgJSLnlR4x_jf6v6y_srKN8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1916107927</pqid></control><display><type>article</type><title>Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression</title><source>MEDLINE</source><source>Springer Online Journals</source><creator>Shimizu, Yoichi ; Hanzawa, Hiroko ; Zhao, Yan ; Fukura, Sagiri ; Nishijima, Ken-ichi ; Sakamoto, Takeshi ; Zhao, Songji ; Tamaki, Nagara ; Ogawa, Mikako ; Kuge, Yuji</creator><creatorcontrib>Shimizu, Yoichi ; Hanzawa, Hiroko ; Zhao, Yan ; Fukura, Sagiri ; Nishijima, Ken-ichi ; Sakamoto, Takeshi ; Zhao, Songji ; Tamaki, Nagara ; Ogawa, Mikako ; Kuge, Yuji</creatorcontrib><description>Purpose
Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis. However, IgG accumulates nonspecifically in atherosclerotic regions, and its accumulation mechanisms have not yet been clarified in detail. Therefore, we explored IgG accumulation mechanisms in atherosclerotic lesions and examined images of radiolabeled IgG for the diagnosis of atherosclerosis.
Procedures
Mouse IgG without specificity to biomolecules was labeled with technetium-99m via 6-hydrazinonicotinate to yield [
99m
Tc]IgG. ApoE
−/−
or C57BL/6J mice were injected intravenously with [
99m
Tc]IgG, and their aortas were excised 24 h after injection. After radioactivity measurement, serial aortic sections were autoradiographically and histopathologically examined. RAW264.7 macrophages were polarized into M1 or M2 and then treated with [
99m
Tc]IgG. The radioactivities in the cells were measured after 1 h of incubation. [
99m
Tc]IgG uptake in M1 macrophages was also evaluated after the pretreatment with an anti-Fcγ receptor (FcγR) antibody. The expression levels of FcγRs in the cells were measured by western blot analysis.
Results
[
99m
Tc]IgG accumulation levels in the aortas were significantly higher in apoE
−/−
mice than in C57BL/6J mice (5.1 ± 1.4 vs 2.8 ± 0.5 %ID/g,
p
< 0.05). Autoradiographic images showed that the accumulation areas highly correlated with the macrophage-infiltrated areas. M1 macrophages showed significantly higher levels of [
99m
Tc]IgG than M2 or M0 (nonpolarized) macrophages [2.2 ± 0.3 (M1) vs 0.5 ± 0.1 (M2), 0.4 ± 0.1 (M0) %dose/mg protein,
p
< 0.01] and higher expression levels of FcγRI and FcγRII. [
99m
Tc]IgG accumulation in M1 macrophages was suppressed by pretreatment with the anti-FcγR antibody [2.2 ± 0.3 (nonpretreatment) vs 1.2 ± 0.2 (pretreatment) %ID/mg protein,
p
< 0.01].
Conclusions
IgG accumulated in pro-inflammatory M1 macrophages via FcγRs in atherosclerotic lesions. Thus, the target biomolecule-independent imaging of active inflammation should be taken into account in the diagnosis of atherosclerosis using IgG-based probes.</description><identifier>ISSN: 1536-1632</identifier><identifier>EISSN: 1860-2002</identifier><identifier>DOI: 10.1007/s11307-016-1036-8</identifier><identifier>PMID: 27981470</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Accumulation ; Animals ; Aorta ; Apolipoprotein E ; Apolipoproteins E - deficiency ; Apolipoproteins E - metabolism ; Arteriosclerosis ; Atherosclerosis ; Autoradiography ; Biomolecules ; Cell Polarity ; Diagnosis ; Imaging ; Immunoglobulin G ; Immunoglobulin G - metabolism ; Immunoglobulins ; Inflammation ; Ischemia ; Lesions ; Macrophages ; Macrophages - metabolism ; Macrophages - pathology ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred C57BL ; Molecular Imaging - methods ; Molecular Probes - metabolism ; Nitric Oxide Synthase Type II - metabolism ; Plaque, Atherosclerotic - pathology ; Plaques ; Probes ; Radioactivity ; Radiology ; RAW 264.7 Cells ; Receptors, IgG - metabolism ; Research Article ; Target recognition ; Technetium ; Technetium - metabolism ; Tissue Distribution</subject><ispartof>Molecular imaging and biology, 2017-08, Vol.19 (4), p.531-539</ispartof><rights>World Molecular Imaging Society 2016</rights><rights>Molecular Imaging and Biology is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-71023f405ca79ef8826d7cc108626b28d7bffa2bfe4e7bb5101437e96e9f486d3</citedby><cites>FETCH-LOGICAL-c525t-71023f405ca79ef8826d7cc108626b28d7bffa2bfe4e7bb5101437e96e9f486d3</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/s11307-016-1036-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11307-016-1036-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27981470$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shimizu, Yoichi</creatorcontrib><creatorcontrib>Hanzawa, Hiroko</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Fukura, Sagiri</creatorcontrib><creatorcontrib>Nishijima, Ken-ichi</creatorcontrib><creatorcontrib>Sakamoto, Takeshi</creatorcontrib><creatorcontrib>Zhao, Songji</creatorcontrib><creatorcontrib>Tamaki, Nagara</creatorcontrib><creatorcontrib>Ogawa, Mikako</creatorcontrib><creatorcontrib>Kuge, Yuji</creatorcontrib><title>Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression</title><title>Molecular imaging and biology</title><addtitle>Mol Imaging Biol</addtitle><addtitle>Mol Imaging Biol</addtitle><description>Purpose
Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis. However, IgG accumulates nonspecifically in atherosclerotic regions, and its accumulation mechanisms have not yet been clarified in detail. Therefore, we explored IgG accumulation mechanisms in atherosclerotic lesions and examined images of radiolabeled IgG for the diagnosis of atherosclerosis.
Procedures
Mouse IgG without specificity to biomolecules was labeled with technetium-99m via 6-hydrazinonicotinate to yield [
99m
Tc]IgG. ApoE
−/−
or C57BL/6J mice were injected intravenously with [
99m
Tc]IgG, and their aortas were excised 24 h after injection. After radioactivity measurement, serial aortic sections were autoradiographically and histopathologically examined. RAW264.7 macrophages were polarized into M1 or M2 and then treated with [
99m
Tc]IgG. The radioactivities in the cells were measured after 1 h of incubation. [
99m
Tc]IgG uptake in M1 macrophages was also evaluated after the pretreatment with an anti-Fcγ receptor (FcγR) antibody. The expression levels of FcγRs in the cells were measured by western blot analysis.
Results
[
99m
Tc]IgG accumulation levels in the aortas were significantly higher in apoE
−/−
mice than in C57BL/6J mice (5.1 ± 1.4 vs 2.8 ± 0.5 %ID/g,
p
< 0.05). Autoradiographic images showed that the accumulation areas highly correlated with the macrophage-infiltrated areas. M1 macrophages showed significantly higher levels of [
99m
Tc]IgG than M2 or M0 (nonpolarized) macrophages [2.2 ± 0.3 (M1) vs 0.5 ± 0.1 (M2), 0.4 ± 0.1 (M0) %dose/mg protein,
p
< 0.01] and higher expression levels of FcγRI and FcγRII. [
99m
Tc]IgG accumulation in M1 macrophages was suppressed by pretreatment with the anti-FcγR antibody [2.2 ± 0.3 (nonpretreatment) vs 1.2 ± 0.2 (pretreatment) %ID/mg protein,
p
< 0.01].
Conclusions
IgG accumulated in pro-inflammatory M1 macrophages via FcγRs in atherosclerotic lesions. Thus, the target biomolecule-independent imaging of active inflammation should be taken into account in the diagnosis of atherosclerosis using IgG-based probes.</description><subject>Accumulation</subject><subject>Animals</subject><subject>Aorta</subject><subject>Apolipoprotein E</subject><subject>Apolipoproteins E - deficiency</subject><subject>Apolipoproteins E - metabolism</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Autoradiography</subject><subject>Biomolecules</subject><subject>Cell Polarity</subject><subject>Diagnosis</subject><subject>Imaging</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - metabolism</subject><subject>Immunoglobulins</subject><subject>Inflammation</subject><subject>Ischemia</subject><subject>Lesions</subject><subject>Macrophages</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - pathology</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Imaging - methods</subject><subject>Molecular Probes - metabolism</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Plaque, Atherosclerotic - pathology</subject><subject>Plaques</subject><subject>Probes</subject><subject>Radioactivity</subject><subject>Radiology</subject><subject>RAW 264.7 Cells</subject><subject>Receptors, IgG - metabolism</subject><subject>Research Article</subject><subject>Target recognition</subject><subject>Technetium</subject><subject>Technetium - metabolism</subject><subject>Tissue Distribution</subject><issn>1536-1632</issn><issn>1860-2002</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kcFu1DAQhiMEoqXwAFyQJS7lEPA4ie0cl6oskbqih3K2HGecpnLsYCcSPApvi1dbEELiMrY83__PyH9RvAb6HigVHxJARUVJgZdAK17KJ8U5SE5LRil7mu9NfgResbPiRUoPlIIAVj0vzphoJdSCnhc_u3nefBhd6Dc3ebInl924f1d-1AkH0s16nPxIbmPokeyM2ebN6RUTyegByEGbGJZ7PWLZeTu5NebmQHbrPcaQjMt1nQy5dfrblkWdH3DBXPxKgiV5ELnTccSVHIJDszkk19-XiClNwb8snlntEr56PC-Kr5-u764-lzdf9t3V7qY0DWvWUgBlla1pY7Ro0UrJ-CCMASo54z2Tg-it1ay3WKPo-wYo1JXAlmNra8mH6qK4PPkuMRy3XNU8JYPOaY9hSwpkw7iUbdtm9O0_6EPYos_bKWiBAxUtE5mCE5X_JqWIVi1xmnX8oYCqY27qlJvKualjbkpmzZtH562fcfij-B1UBtgJSLnlR4x_jf6v6y_srKN8</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Shimizu, Yoichi</creator><creator>Hanzawa, Hiroko</creator><creator>Zhao, Yan</creator><creator>Fukura, Sagiri</creator><creator>Nishijima, Ken-ichi</creator><creator>Sakamoto, Takeshi</creator><creator>Zhao, Songji</creator><creator>Tamaki, Nagara</creator><creator>Ogawa, Mikako</creator><creator>Kuge, Yuji</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7QO</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>L6V</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>7X8</scope></search><sort><creationdate>20170801</creationdate><title>Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression</title><author>Shimizu, Yoichi ; Hanzawa, Hiroko ; Zhao, Yan ; Fukura, Sagiri ; Nishijima, Ken-ichi ; Sakamoto, Takeshi ; Zhao, Songji ; Tamaki, Nagara ; Ogawa, Mikako ; Kuge, Yuji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-71023f405ca79ef8826d7cc108626b28d7bffa2bfe4e7bb5101437e96e9f486d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Accumulation</topic><topic>Animals</topic><topic>Aorta</topic><topic>Apolipoprotein E</topic><topic>Apolipoproteins E - deficiency</topic><topic>Apolipoproteins E - metabolism</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Autoradiography</topic><topic>Biomolecules</topic><topic>Cell Polarity</topic><topic>Diagnosis</topic><topic>Imaging</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin G - metabolism</topic><topic>Immunoglobulins</topic><topic>Inflammation</topic><topic>Ischemia</topic><topic>Lesions</topic><topic>Macrophages</topic><topic>Macrophages - metabolism</topic><topic>Macrophages - pathology</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Imaging - methods</topic><topic>Molecular Probes - metabolism</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Plaque, Atherosclerotic - pathology</topic><topic>Plaques</topic><topic>Probes</topic><topic>Radioactivity</topic><topic>Radiology</topic><topic>RAW 264.7 Cells</topic><topic>Receptors, IgG - metabolism</topic><topic>Research Article</topic><topic>Target recognition</topic><topic>Technetium</topic><topic>Technetium - metabolism</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shimizu, Yoichi</creatorcontrib><creatorcontrib>Hanzawa, Hiroko</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Fukura, Sagiri</creatorcontrib><creatorcontrib>Nishijima, Ken-ichi</creatorcontrib><creatorcontrib>Sakamoto, Takeshi</creatorcontrib><creatorcontrib>Zhao, Songji</creatorcontrib><creatorcontrib>Tamaki, Nagara</creatorcontrib><creatorcontrib>Ogawa, Mikako</creatorcontrib><creatorcontrib>Kuge, Yuji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</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>Technology Research Database</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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</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>Engineering Research Database</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 Engineering Collection</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>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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>Engineering Collection</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular imaging and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shimizu, Yoichi</au><au>Hanzawa, Hiroko</au><au>Zhao, Yan</au><au>Fukura, Sagiri</au><au>Nishijima, Ken-ichi</au><au>Sakamoto, Takeshi</au><au>Zhao, Songji</au><au>Tamaki, Nagara</au><au>Ogawa, Mikako</au><au>Kuge, Yuji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression</atitle><jtitle>Molecular imaging and biology</jtitle><stitle>Mol Imaging Biol</stitle><addtitle>Mol Imaging Biol</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>19</volume><issue>4</issue><spage>531</spage><epage>539</epage><pages>531-539</pages><issn>1536-1632</issn><eissn>1860-2002</eissn><abstract>Purpose
Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis. However, IgG accumulates nonspecifically in atherosclerotic regions, and its accumulation mechanisms have not yet been clarified in detail. Therefore, we explored IgG accumulation mechanisms in atherosclerotic lesions and examined images of radiolabeled IgG for the diagnosis of atherosclerosis.
Procedures
Mouse IgG without specificity to biomolecules was labeled with technetium-99m via 6-hydrazinonicotinate to yield [
99m
Tc]IgG. ApoE
−/−
or C57BL/6J mice were injected intravenously with [
99m
Tc]IgG, and their aortas were excised 24 h after injection. After radioactivity measurement, serial aortic sections were autoradiographically and histopathologically examined. RAW264.7 macrophages were polarized into M1 or M2 and then treated with [
99m
Tc]IgG. The radioactivities in the cells were measured after 1 h of incubation. [
99m
Tc]IgG uptake in M1 macrophages was also evaluated after the pretreatment with an anti-Fcγ receptor (FcγR) antibody. The expression levels of FcγRs in the cells were measured by western blot analysis.
Results
[
99m
Tc]IgG accumulation levels in the aortas were significantly higher in apoE
−/−
mice than in C57BL/6J mice (5.1 ± 1.4 vs 2.8 ± 0.5 %ID/g,
p
< 0.05). Autoradiographic images showed that the accumulation areas highly correlated with the macrophage-infiltrated areas. M1 macrophages showed significantly higher levels of [
99m
Tc]IgG than M2 or M0 (nonpolarized) macrophages [2.2 ± 0.3 (M1) vs 0.5 ± 0.1 (M2), 0.4 ± 0.1 (M0) %dose/mg protein,
p
< 0.01] and higher expression levels of FcγRI and FcγRII. [
99m
Tc]IgG accumulation in M1 macrophages was suppressed by pretreatment with the anti-FcγR antibody [2.2 ± 0.3 (nonpretreatment) vs 1.2 ± 0.2 (pretreatment) %ID/mg protein,
p
< 0.01].
Conclusions
IgG accumulated in pro-inflammatory M1 macrophages via FcγRs in atherosclerotic lesions. Thus, the target biomolecule-independent imaging of active inflammation should be taken into account in the diagnosis of atherosclerosis using IgG-based probes.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>27981470</pmid><doi>10.1007/s11307-016-1036-8</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1536-1632 |
| ispartof | Molecular imaging and biology, 2017-08, Vol.19 (4), p.531-539 |
| issn | 1536-1632 1860-2002 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1852688999 |
| source | MEDLINE; Springer Online Journals |
| subjects | Accumulation Animals Aorta Apolipoprotein E Apolipoproteins E - deficiency Apolipoproteins E - metabolism Arteriosclerosis Atherosclerosis Autoradiography Biomolecules Cell Polarity Diagnosis Imaging Immunoglobulin G Immunoglobulin G - metabolism Immunoglobulins Inflammation Ischemia Lesions Macrophages Macrophages - metabolism Macrophages - pathology Medicine Medicine & Public Health Mice Mice, Inbred C57BL Molecular Imaging - methods Molecular Probes - metabolism Nitric Oxide Synthase Type II - metabolism Plaque, Atherosclerotic - pathology Plaques Probes Radioactivity Radiology RAW 264.7 Cells Receptors, IgG - metabolism Research Article Target recognition Technetium Technetium - metabolism Tissue Distribution |
| title | Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T19%3A32%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Immunoglobulin%20G%20(IgG)-Based%20Imaging%20Probe%20Accumulates%20in%20M1%20Macrophage-Infiltrated%20Atherosclerotic%20Plaques%20Independent%20of%20IgG%20Target%20Molecule%20Expression&rft.jtitle=Molecular%20imaging%20and%20biology&rft.au=Shimizu,%20Yoichi&rft.date=2017-08-01&rft.volume=19&rft.issue=4&rft.spage=531&rft.epage=539&rft.pages=531-539&rft.issn=1536-1632&rft.eissn=1860-2002&rft_id=info:doi/10.1007/s11307-016-1036-8&rft_dat=%3Cproquest_cross%3E1852688999%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1916107927&rft_id=info:pmid/27981470&rfr_iscdi=true |