sup 18^F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis
Immune cell–mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers th...
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| Veröffentlicht in: | The Journal of nuclear medicine (1978) 2018-10, Vol.59 (10), p.1616 |
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| creator | Salas, Jessica R Chen, Bao Ying Cheng, Donghui Wong, Alicia Witte, Owen N Van Arnam, John S Clark, Peter M |
| description | Immune cell–mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation (£sup£18¥sup¥F-FDG and £sup£18¥sup¥F-1-(2′-deoxy-2′-fluoro-arabinofuranosyl)cytosine [£sup£18¥sup¥F-FAC]) and hepatocyte biology (£sup£18¥sup¥F-2-deoxy-2-fluoroarabinose [£sup£18¥sup¥F-DFA]) can visualize and quantify liver-infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis. Methods: Mice treated with concanavalin A (ConA) to induce a model of autoimmune hepatitis or vehicle were imaged with £sup£18¥sup¥F-FDG, £sup£18¥sup¥F-FAC, and £sup£18¥sup¥F-DFA PET. Immunohistochemistry, digital autoradiography, and ex vivo accumulation assays were used to localize areas of altered radiotracer accumulation in the liver. For comparison, mice treated with an adenovirus to induce a viral hepatitis were imaged with £sup£18¥sup¥F-FDG, £sup£18¥sup¥F-FAC, and £sup£18¥sup¥F-DFA PET. £sup£18¥sup¥F-FAC PET was performed on mice treated with ConA and vehicle or with ConA and dexamethasone. Biopsy samples of patients with autoimmune hepatitis were immunostained for deoxycytidine kinase. Results: Hepatic accumulation of £sup£18¥sup¥F-FDG and £sup£18¥sup¥F-FAC was 173% and 61% higher, respectively, and hepatic accumulation of £sup£18¥sup¥F-DFA was 41% lower, in a mouse model of autoimmune hepatitis than in control mice. Increased hepatic £sup£18¥sup¥F-FDG accumulation was localized to infiltrating leukocytes and inflamed sinusoidal endothelial cells, increased hepatic £sup£18¥sup¥F-FAC accumulation was concentrated in infiltrating CD4 and CD8 cells, and decreased hepatic £sup£18¥sup¥F-DFA accumulation was apparent in hepatocytes throughout the liver. In contrast, viral hepatitis increased hepatic £sup£18¥sup¥F-FDG accumulation by 109% and decreased hepatic £sup£18¥sup¥F-DFA accumulation by 20% but had no effect on hepatic £sup£18¥sup¥F-FAC accumulation (nonsignificant 2% decrease). £sup£18¥sup¥F-FAC PET provided a noninvasive biomarker of the efficacy of dexamethasone for treating the autoimmune hepatitis model. Infiltrating leukocytes in liver biopsy samples from patients with autoimmune hepatitis express high levels of deoxycytidine kinase, a rate-limiting enzyme in the accumulation of £sup£ |
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| fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_journals_2124786431</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2124786431</sourcerecordid><originalsourceid>FETCH-proquest_journals_21247864313</originalsourceid><addsrcrecordid>eNqNi8FqwzAQREVoIW7Tf1joWSDFlqJrcGISaKFQnxtEsg4KsuR4pUL_vjr0A3qZx_BmFqySqlZcab15YJWQWnKlhFqyJ6KbEEIbYypGlCeQ5qvj3baFj30Pn-jxnNw3-h84jvaKBG-lzfwYBufTbJMLV2h3DdhwKTTQQ4veE7gAFt5jJix5QQ9xgG1O0Y1jDggHnMo3OVqxx8F6wpc_PrPXbt-3Bz7N8Z6R0ukW8xyKOq3lutkY3dSy_t_qF8FbSbc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2124786431</pqid></control><display><type>article</type><title>sup 18^F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis</title><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>Salas, Jessica R ; Chen, Bao Ying ; Cheng, Donghui ; Wong, Alicia ; Witte, Owen N ; Van Arnam, John S ; Clark, Peter M</creator><creatorcontrib>Salas, Jessica R ; Chen, Bao Ying ; Cheng, Donghui ; Wong, Alicia ; Witte, Owen N ; Van Arnam, John S ; Clark, Peter M</creatorcontrib><description>Immune cell–mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation (£sup£18¥sup¥F-FDG and £sup£18¥sup¥F-1-(2′-deoxy-2′-fluoro-arabinofuranosyl)cytosine [£sup£18¥sup¥F-FAC]) and hepatocyte biology (£sup£18¥sup¥F-2-deoxy-2-fluoroarabinose [£sup£18¥sup¥F-DFA]) can visualize and quantify liver-infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis. Methods: Mice treated with concanavalin A (ConA) to induce a model of autoimmune hepatitis or vehicle were imaged with £sup£18¥sup¥F-FDG, £sup£18¥sup¥F-FAC, and £sup£18¥sup¥F-DFA PET. Immunohistochemistry, digital autoradiography, and ex vivo accumulation assays were used to localize areas of altered radiotracer accumulation in the liver. For comparison, mice treated with an adenovirus to induce a viral hepatitis were imaged with £sup£18¥sup¥F-FDG, £sup£18¥sup¥F-FAC, and £sup£18¥sup¥F-DFA PET. £sup£18¥sup¥F-FAC PET was performed on mice treated with ConA and vehicle or with ConA and dexamethasone. Biopsy samples of patients with autoimmune hepatitis were immunostained for deoxycytidine kinase. Results: Hepatic accumulation of £sup£18¥sup¥F-FDG and £sup£18¥sup¥F-FAC was 173% and 61% higher, respectively, and hepatic accumulation of £sup£18¥sup¥F-DFA was 41% lower, in a mouse model of autoimmune hepatitis than in control mice. Increased hepatic £sup£18¥sup¥F-FDG accumulation was localized to infiltrating leukocytes and inflamed sinusoidal endothelial cells, increased hepatic £sup£18¥sup¥F-FAC accumulation was concentrated in infiltrating CD4 and CD8 cells, and decreased hepatic £sup£18¥sup¥F-DFA accumulation was apparent in hepatocytes throughout the liver. In contrast, viral hepatitis increased hepatic £sup£18¥sup¥F-FDG accumulation by 109% and decreased hepatic £sup£18¥sup¥F-DFA accumulation by 20% but had no effect on hepatic £sup£18¥sup¥F-FAC accumulation (nonsignificant 2% decrease). £sup£18¥sup¥F-FAC PET provided a noninvasive biomarker of the efficacy of dexamethasone for treating the autoimmune hepatitis model. Infiltrating leukocytes in liver biopsy samples from patients with autoimmune hepatitis express high levels of deoxycytidine kinase, a rate-limiting enzyme in the accumulation of £sup£18¥sup¥F-FAC. Conclusion: Our data suggest that PET can be used to noninvasively visualize activated leukocytes and inflamed hepatocytes in a mouse model of autoimmune hepatitis.</description><identifier>ISSN: 0161-5505</identifier><identifier>EISSN: 1535-5667</identifier><language>eng</language><publisher>New York: Society of Nuclear Medicine</publisher><subject>Accumulation ; Autoimmune diseases ; Autoradiography ; Biomarkers ; Biopsy ; CD4 antigen ; CD8 antigen ; Concanavalin A ; Cytosine ; Deoxycytidine kinase ; Dexamethasone ; Diagnostic software ; Diagnostic systems ; Endothelial cells ; Graft rejection ; Hepatitis ; Hepatocytes ; Immune system ; Immunohistochemistry ; Inflammation ; Leukocytes ; Liver ; Liver transplantation ; Lymphocytes T ; Medical imaging ; Mice ; Patients ; Positron emission ; Positron emission tomography ; Radioactive tracers ; Rodents ; T cell receptors ; Tomography</subject><ispartof>The Journal of nuclear medicine (1978), 2018-10, Vol.59 (10), p.1616</ispartof><rights>Copyright Society of Nuclear Medicine Oct 1, 2018</rights><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>314,777,781</link.rule.ids></links><search><creatorcontrib>Salas, Jessica R</creatorcontrib><creatorcontrib>Chen, Bao Ying</creatorcontrib><creatorcontrib>Cheng, Donghui</creatorcontrib><creatorcontrib>Wong, Alicia</creatorcontrib><creatorcontrib>Witte, Owen N</creatorcontrib><creatorcontrib>Van Arnam, John S</creatorcontrib><creatorcontrib>Clark, Peter M</creatorcontrib><title>sup 18^F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis</title><title>The Journal of nuclear medicine (1978)</title><description>Immune cell–mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation (£sup£18¥sup¥F-FDG and £sup£18¥sup¥F-1-(2′-deoxy-2′-fluoro-arabinofuranosyl)cytosine [£sup£18¥sup¥F-FAC]) and hepatocyte biology (£sup£18¥sup¥F-2-deoxy-2-fluoroarabinose [£sup£18¥sup¥F-DFA]) can visualize and quantify liver-infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis. Methods: Mice treated with concanavalin A (ConA) to induce a model of autoimmune hepatitis or vehicle were imaged with £sup£18¥sup¥F-FDG, £sup£18¥sup¥F-FAC, and £sup£18¥sup¥F-DFA PET. Immunohistochemistry, digital autoradiography, and ex vivo accumulation assays were used to localize areas of altered radiotracer accumulation in the liver. For comparison, mice treated with an adenovirus to induce a viral hepatitis were imaged with £sup£18¥sup¥F-FDG, £sup£18¥sup¥F-FAC, and £sup£18¥sup¥F-DFA PET. £sup£18¥sup¥F-FAC PET was performed on mice treated with ConA and vehicle or with ConA and dexamethasone. Biopsy samples of patients with autoimmune hepatitis were immunostained for deoxycytidine kinase. Results: Hepatic accumulation of £sup£18¥sup¥F-FDG and £sup£18¥sup¥F-FAC was 173% and 61% higher, respectively, and hepatic accumulation of £sup£18¥sup¥F-DFA was 41% lower, in a mouse model of autoimmune hepatitis than in control mice. Increased hepatic £sup£18¥sup¥F-FDG accumulation was localized to infiltrating leukocytes and inflamed sinusoidal endothelial cells, increased hepatic £sup£18¥sup¥F-FAC accumulation was concentrated in infiltrating CD4 and CD8 cells, and decreased hepatic £sup£18¥sup¥F-DFA accumulation was apparent in hepatocytes throughout the liver. In contrast, viral hepatitis increased hepatic £sup£18¥sup¥F-FDG accumulation by 109% and decreased hepatic £sup£18¥sup¥F-DFA accumulation by 20% but had no effect on hepatic £sup£18¥sup¥F-FAC accumulation (nonsignificant 2% decrease). £sup£18¥sup¥F-FAC PET provided a noninvasive biomarker of the efficacy of dexamethasone for treating the autoimmune hepatitis model. Infiltrating leukocytes in liver biopsy samples from patients with autoimmune hepatitis express high levels of deoxycytidine kinase, a rate-limiting enzyme in the accumulation of £sup£18¥sup¥F-FAC. Conclusion: Our data suggest that PET can be used to noninvasively visualize activated leukocytes and inflamed hepatocytes in a mouse model of autoimmune hepatitis.</description><subject>Accumulation</subject><subject>Autoimmune diseases</subject><subject>Autoradiography</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Concanavalin A</subject><subject>Cytosine</subject><subject>Deoxycytidine kinase</subject><subject>Dexamethasone</subject><subject>Diagnostic software</subject><subject>Diagnostic systems</subject><subject>Endothelial cells</subject><subject>Graft rejection</subject><subject>Hepatitis</subject><subject>Hepatocytes</subject><subject>Immune system</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Leukocytes</subject><subject>Liver</subject><subject>Liver transplantation</subject><subject>Lymphocytes T</subject><subject>Medical imaging</subject><subject>Mice</subject><subject>Patients</subject><subject>Positron emission</subject><subject>Positron emission tomography</subject><subject>Radioactive tracers</subject><subject>Rodents</subject><subject>T cell receptors</subject><subject>Tomography</subject><issn>0161-5505</issn><issn>1535-5667</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqNi8FqwzAQREVoIW7Tf1joWSDFlqJrcGISaKFQnxtEsg4KsuR4pUL_vjr0A3qZx_BmFqySqlZcab15YJWQWnKlhFqyJ6KbEEIbYypGlCeQ5qvj3baFj30Pn-jxnNw3-h84jvaKBG-lzfwYBufTbJMLV2h3DdhwKTTQQ4veE7gAFt5jJix5QQ9xgG1O0Y1jDggHnMo3OVqxx8F6wpc_PrPXbt-3Bz7N8Z6R0ukW8xyKOq3lutkY3dSy_t_qF8FbSbc</recordid><startdate>20181001</startdate><enddate>20181001</enddate><creator>Salas, Jessica R</creator><creator>Chen, Bao Ying</creator><creator>Cheng, Donghui</creator><creator>Wong, Alicia</creator><creator>Witte, Owen N</creator><creator>Van Arnam, John S</creator><creator>Clark, Peter M</creator><general>Society of Nuclear Medicine</general><scope>4T-</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7Z</scope><scope>NAPCQ</scope><scope>P64</scope></search><sort><creationdate>20181001</creationdate><title>sup 18^F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis</title><author>Salas, Jessica R ; Chen, Bao Ying ; Cheng, Donghui ; Wong, Alicia ; Witte, Owen N ; Van Arnam, John S ; Clark, Peter M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_21247864313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Accumulation</topic><topic>Autoimmune diseases</topic><topic>Autoradiography</topic><topic>Biomarkers</topic><topic>Biopsy</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Concanavalin A</topic><topic>Cytosine</topic><topic>Deoxycytidine kinase</topic><topic>Dexamethasone</topic><topic>Diagnostic software</topic><topic>Diagnostic systems</topic><topic>Endothelial cells</topic><topic>Graft rejection</topic><topic>Hepatitis</topic><topic>Hepatocytes</topic><topic>Immune system</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Leukocytes</topic><topic>Liver</topic><topic>Liver transplantation</topic><topic>Lymphocytes T</topic><topic>Medical imaging</topic><topic>Mice</topic><topic>Patients</topic><topic>Positron emission</topic><topic>Positron emission tomography</topic><topic>Radioactive tracers</topic><topic>Rodents</topic><topic>T cell receptors</topic><topic>Tomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Salas, Jessica R</creatorcontrib><creatorcontrib>Chen, Bao Ying</creatorcontrib><creatorcontrib>Cheng, Donghui</creatorcontrib><creatorcontrib>Wong, Alicia</creatorcontrib><creatorcontrib>Witte, Owen N</creatorcontrib><creatorcontrib>Van Arnam, John S</creatorcontrib><creatorcontrib>Clark, Peter M</creatorcontrib><collection>Docstoc</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biochemistry Abstracts 1</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>The Journal of nuclear medicine (1978)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salas, Jessica R</au><au>Chen, Bao Ying</au><au>Cheng, Donghui</au><au>Wong, Alicia</au><au>Witte, Owen N</au><au>Van Arnam, John S</au><au>Clark, Peter M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>sup 18^F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis</atitle><jtitle>The Journal of nuclear medicine (1978)</jtitle><date>2018-10-01</date><risdate>2018</risdate><volume>59</volume><issue>10</issue><spage>1616</spage><pages>1616-</pages><issn>0161-5505</issn><eissn>1535-5667</eissn><abstract>Immune cell–mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation (£sup£18¥sup¥F-FDG and £sup£18¥sup¥F-1-(2′-deoxy-2′-fluoro-arabinofuranosyl)cytosine [£sup£18¥sup¥F-FAC]) and hepatocyte biology (£sup£18¥sup¥F-2-deoxy-2-fluoroarabinose [£sup£18¥sup¥F-DFA]) can visualize and quantify liver-infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis. Methods: Mice treated with concanavalin A (ConA) to induce a model of autoimmune hepatitis or vehicle were imaged with £sup£18¥sup¥F-FDG, £sup£18¥sup¥F-FAC, and £sup£18¥sup¥F-DFA PET. Immunohistochemistry, digital autoradiography, and ex vivo accumulation assays were used to localize areas of altered radiotracer accumulation in the liver. For comparison, mice treated with an adenovirus to induce a viral hepatitis were imaged with £sup£18¥sup¥F-FDG, £sup£18¥sup¥F-FAC, and £sup£18¥sup¥F-DFA PET. £sup£18¥sup¥F-FAC PET was performed on mice treated with ConA and vehicle or with ConA and dexamethasone. Biopsy samples of patients with autoimmune hepatitis were immunostained for deoxycytidine kinase. Results: Hepatic accumulation of £sup£18¥sup¥F-FDG and £sup£18¥sup¥F-FAC was 173% and 61% higher, respectively, and hepatic accumulation of £sup£18¥sup¥F-DFA was 41% lower, in a mouse model of autoimmune hepatitis than in control mice. Increased hepatic £sup£18¥sup¥F-FDG accumulation was localized to infiltrating leukocytes and inflamed sinusoidal endothelial cells, increased hepatic £sup£18¥sup¥F-FAC accumulation was concentrated in infiltrating CD4 and CD8 cells, and decreased hepatic £sup£18¥sup¥F-DFA accumulation was apparent in hepatocytes throughout the liver. In contrast, viral hepatitis increased hepatic £sup£18¥sup¥F-FDG accumulation by 109% and decreased hepatic £sup£18¥sup¥F-DFA accumulation by 20% but had no effect on hepatic £sup£18¥sup¥F-FAC accumulation (nonsignificant 2% decrease). £sup£18¥sup¥F-FAC PET provided a noninvasive biomarker of the efficacy of dexamethasone for treating the autoimmune hepatitis model. Infiltrating leukocytes in liver biopsy samples from patients with autoimmune hepatitis express high levels of deoxycytidine kinase, a rate-limiting enzyme in the accumulation of £sup£18¥sup¥F-FAC. Conclusion: Our data suggest that PET can be used to noninvasively visualize activated leukocytes and inflamed hepatocytes in a mouse model of autoimmune hepatitis.</abstract><cop>New York</cop><pub>Society of Nuclear Medicine</pub></addata></record> |
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| subjects | Accumulation Autoimmune diseases Autoradiography Biomarkers Biopsy CD4 antigen CD8 antigen Concanavalin A Cytosine Deoxycytidine kinase Dexamethasone Diagnostic software Diagnostic systems Endothelial cells Graft rejection Hepatitis Hepatocytes Immune system Immunohistochemistry Inflammation Leukocytes Liver Liver transplantation Lymphocytes T Medical imaging Mice Patients Positron emission Positron emission tomography Radioactive tracers Rodents T cell receptors Tomography |
| title | sup 18^F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis |
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