Assessment of Inflammation in Pulmonary Artery Hypertension by 68 Ga-Mannosylated Human Serum Albumin
Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult. We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent, Ga-2-( -isoth...
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| Veröffentlicht in: | American journal of respiratory and critical care medicine 2020-01, Vol.201 (1), p.95-106 |
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| creator | Park, Jun-Bean Suh, Minseok Park, Ji Yong Park, Jin Kyun Kim, Yong-Il Kim, Hyunah Cho, Ye Seul Kang, Hyejeong Kim, Kibyung Choi, Jae-Hoon Nam, Jin-Wu Kim, Hyung-Kwan Lee, Yun-Sang Jeong, Jae Min Kim, Yong-Jin Paeng, Jin Chul Lee, Seung-Pyo |
| description | Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.
We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent,
Ga-2-(
-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).
We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and
Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of
Ga-NOTA-MSA PET was explored in patients with PAH.
Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of
Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of
Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of
Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (
= 0.009) or than those with pulmonary hypertension by left heart disease (
= 0.019) (
= 5 per group).
Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that
Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH. |
| doi_str_mv | 10.1164/rccm.201903-0639OC |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1164_rccm_201903_0639OC</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>31322420</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1150-6b6716c20ae05a0e17dffbe4c5bd861d1e39e0117a89192e96e587d1e53be1923</originalsourceid><addsrcrecordid>eNo9kEFLw0AQhRdRbK3-AQ-yfyB1ZjfZZI-haFuoVFDBW9gkE4hkNyWbHPLvTUn19B6P94bhY-wRYY2owueuKOxaAGqQASipj5srtsRIRkGoY7iePMQyCEP9vWB33v8AoEgQbtlCohQiFLBklHpP3ltyPW8rvndVY6w1fd06Xjv-PjS2daYbedr1NMluPNHknD8X8pGrhG9N8Gaca_3YmJ5KvhuscfyDusHytMkHW7t7dlOZxtPDRVfs6_Xlc7MLDsftfpMeggIxgkDlKkZVCDAEkQHCuKyqnMIiystEYYkkNQFibBKNWpBWFCXxFEcypymQKybmu0XXet9RlZ262k7vZwjZmVl2ZpbNzLKZ2TR6mkenIbdU_k_-IMlfuY9paQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Assessment of Inflammation in Pulmonary Artery Hypertension by 68 Ga-Mannosylated Human Serum Albumin</title><source>MEDLINE</source><source>American Thoracic Society (ATS) Journals Online</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Park, Jun-Bean ; Suh, Minseok ; Park, Ji Yong ; Park, Jin Kyun ; Kim, Yong-Il ; Kim, Hyunah ; Cho, Ye Seul ; Kang, Hyejeong ; Kim, Kibyung ; Choi, Jae-Hoon ; Nam, Jin-Wu ; Kim, Hyung-Kwan ; Lee, Yun-Sang ; Jeong, Jae Min ; Kim, Yong-Jin ; Paeng, Jin Chul ; Lee, Seung-Pyo</creator><creatorcontrib>Park, Jun-Bean ; Suh, Minseok ; Park, Ji Yong ; Park, Jin Kyun ; Kim, Yong-Il ; Kim, Hyunah ; Cho, Ye Seul ; Kang, Hyejeong ; Kim, Kibyung ; Choi, Jae-Hoon ; Nam, Jin-Wu ; Kim, Hyung-Kwan ; Lee, Yun-Sang ; Jeong, Jae Min ; Kim, Yong-Jin ; Paeng, Jin Chul ; Lee, Seung-Pyo</creatorcontrib><description>Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.
We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent,
Ga-2-(
-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).
We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and
Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of
Ga-NOTA-MSA PET was explored in patients with PAH.
Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of
Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of
Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of
Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (
= 0.009) or than those with pulmonary hypertension by left heart disease (
= 0.019) (
= 5 per group).
Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that
Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.</description><identifier>ISSN: 1073-449X</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/rccm.201903-0639OC</identifier><identifier>PMID: 31322420</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Humans ; Hypertension, Pulmonary - blood ; Hypertension, Pulmonary - diagnosis ; Hypertension, Pulmonary - physiopathology ; Inflammation - blood ; Inflammation - diagnosis ; Inflammation - physiopathology ; Male ; Models, Animal ; Positron-Emission Tomography - methods ; Pulmonary Artery - physiopathology ; Rats ; Serum Albumin, Human - analysis</subject><ispartof>American journal of respiratory and critical care medicine, 2020-01, Vol.201 (1), p.95-106</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1150-6b6716c20ae05a0e17dffbe4c5bd861d1e39e0117a89192e96e587d1e53be1923</citedby><cites>FETCH-LOGICAL-c1150-6b6716c20ae05a0e17dffbe4c5bd861d1e39e0117a89192e96e587d1e53be1923</cites><orcidid>0000-0002-5502-3977</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4023,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31322420$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Jun-Bean</creatorcontrib><creatorcontrib>Suh, Minseok</creatorcontrib><creatorcontrib>Park, Ji Yong</creatorcontrib><creatorcontrib>Park, Jin Kyun</creatorcontrib><creatorcontrib>Kim, Yong-Il</creatorcontrib><creatorcontrib>Kim, Hyunah</creatorcontrib><creatorcontrib>Cho, Ye Seul</creatorcontrib><creatorcontrib>Kang, Hyejeong</creatorcontrib><creatorcontrib>Kim, Kibyung</creatorcontrib><creatorcontrib>Choi, Jae-Hoon</creatorcontrib><creatorcontrib>Nam, Jin-Wu</creatorcontrib><creatorcontrib>Kim, Hyung-Kwan</creatorcontrib><creatorcontrib>Lee, Yun-Sang</creatorcontrib><creatorcontrib>Jeong, Jae Min</creatorcontrib><creatorcontrib>Kim, Yong-Jin</creatorcontrib><creatorcontrib>Paeng, Jin Chul</creatorcontrib><creatorcontrib>Lee, Seung-Pyo</creatorcontrib><title>Assessment of Inflammation in Pulmonary Artery Hypertension by 68 Ga-Mannosylated Human Serum Albumin</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.
We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent,
Ga-2-(
-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).
We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and
Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of
Ga-NOTA-MSA PET was explored in patients with PAH.
Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of
Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of
Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of
Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (
= 0.009) or than those with pulmonary hypertension by left heart disease (
= 0.019) (
= 5 per group).
Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that
Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.</description><subject>Animals</subject><subject>Humans</subject><subject>Hypertension, Pulmonary - blood</subject><subject>Hypertension, Pulmonary - diagnosis</subject><subject>Hypertension, Pulmonary - physiopathology</subject><subject>Inflammation - blood</subject><subject>Inflammation - diagnosis</subject><subject>Inflammation - physiopathology</subject><subject>Male</subject><subject>Models, Animal</subject><subject>Positron-Emission Tomography - methods</subject><subject>Pulmonary Artery - physiopathology</subject><subject>Rats</subject><subject>Serum Albumin, Human - analysis</subject><issn>1073-449X</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kEFLw0AQhRdRbK3-AQ-yfyB1ZjfZZI-haFuoVFDBW9gkE4hkNyWbHPLvTUn19B6P94bhY-wRYY2owueuKOxaAGqQASipj5srtsRIRkGoY7iePMQyCEP9vWB33v8AoEgQbtlCohQiFLBklHpP3ltyPW8rvndVY6w1fd06Xjv-PjS2daYbedr1NMluPNHknD8X8pGrhG9N8Gaca_3YmJ5KvhuscfyDusHytMkHW7t7dlOZxtPDRVfs6_Xlc7MLDsftfpMeggIxgkDlKkZVCDAEkQHCuKyqnMIiystEYYkkNQFibBKNWpBWFCXxFEcypymQKybmu0XXet9RlZ262k7vZwjZmVl2ZpbNzLKZ2TR6mkenIbdU_k_-IMlfuY9paQ</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Park, Jun-Bean</creator><creator>Suh, Minseok</creator><creator>Park, Ji Yong</creator><creator>Park, Jin Kyun</creator><creator>Kim, Yong-Il</creator><creator>Kim, Hyunah</creator><creator>Cho, Ye Seul</creator><creator>Kang, Hyejeong</creator><creator>Kim, Kibyung</creator><creator>Choi, Jae-Hoon</creator><creator>Nam, Jin-Wu</creator><creator>Kim, Hyung-Kwan</creator><creator>Lee, Yun-Sang</creator><creator>Jeong, Jae Min</creator><creator>Kim, Yong-Jin</creator><creator>Paeng, Jin Chul</creator><creator>Lee, Seung-Pyo</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-5502-3977</orcidid></search><sort><creationdate>20200101</creationdate><title>Assessment of Inflammation in Pulmonary Artery Hypertension by 68 Ga-Mannosylated Human Serum Albumin</title><author>Park, Jun-Bean ; Suh, Minseok ; Park, Ji Yong ; Park, Jin Kyun ; Kim, Yong-Il ; Kim, Hyunah ; Cho, Ye Seul ; Kang, Hyejeong ; Kim, Kibyung ; Choi, Jae-Hoon ; Nam, Jin-Wu ; Kim, Hyung-Kwan ; Lee, Yun-Sang ; Jeong, Jae Min ; Kim, Yong-Jin ; Paeng, Jin Chul ; Lee, Seung-Pyo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1150-6b6716c20ae05a0e17dffbe4c5bd861d1e39e0117a89192e96e587d1e53be1923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Humans</topic><topic>Hypertension, Pulmonary - blood</topic><topic>Hypertension, Pulmonary - diagnosis</topic><topic>Hypertension, Pulmonary - physiopathology</topic><topic>Inflammation - blood</topic><topic>Inflammation - diagnosis</topic><topic>Inflammation - physiopathology</topic><topic>Male</topic><topic>Models, Animal</topic><topic>Positron-Emission Tomography - methods</topic><topic>Pulmonary Artery - physiopathology</topic><topic>Rats</topic><topic>Serum Albumin, Human - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Jun-Bean</creatorcontrib><creatorcontrib>Suh, Minseok</creatorcontrib><creatorcontrib>Park, Ji Yong</creatorcontrib><creatorcontrib>Park, Jin Kyun</creatorcontrib><creatorcontrib>Kim, Yong-Il</creatorcontrib><creatorcontrib>Kim, Hyunah</creatorcontrib><creatorcontrib>Cho, Ye Seul</creatorcontrib><creatorcontrib>Kang, Hyejeong</creatorcontrib><creatorcontrib>Kim, Kibyung</creatorcontrib><creatorcontrib>Choi, Jae-Hoon</creatorcontrib><creatorcontrib>Nam, Jin-Wu</creatorcontrib><creatorcontrib>Kim, Hyung-Kwan</creatorcontrib><creatorcontrib>Lee, Yun-Sang</creatorcontrib><creatorcontrib>Jeong, Jae Min</creatorcontrib><creatorcontrib>Kim, Yong-Jin</creatorcontrib><creatorcontrib>Paeng, Jin Chul</creatorcontrib><creatorcontrib>Lee, Seung-Pyo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Jun-Bean</au><au>Suh, Minseok</au><au>Park, Ji Yong</au><au>Park, Jin Kyun</au><au>Kim, Yong-Il</au><au>Kim, Hyunah</au><au>Cho, Ye Seul</au><au>Kang, Hyejeong</au><au>Kim, Kibyung</au><au>Choi, Jae-Hoon</au><au>Nam, Jin-Wu</au><au>Kim, Hyung-Kwan</au><au>Lee, Yun-Sang</au><au>Jeong, Jae Min</au><au>Kim, Yong-Jin</au><au>Paeng, Jin Chul</au><au>Lee, Seung-Pyo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessment of Inflammation in Pulmonary Artery Hypertension by 68 Ga-Mannosylated Human Serum Albumin</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><addtitle>Am J Respir Crit Care Med</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>201</volume><issue>1</issue><spage>95</spage><epage>106</epage><pages>95-106</pages><issn>1073-449X</issn><eissn>1535-4970</eissn><abstract>Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.
We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent,
Ga-2-(
-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).
We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and
Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of
Ga-NOTA-MSA PET was explored in patients with PAH.
Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of
Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of
Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of
Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (
= 0.009) or than those with pulmonary hypertension by left heart disease (
= 0.019) (
= 5 per group).
Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that
Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.</abstract><cop>United States</cop><pmid>31322420</pmid><doi>10.1164/rccm.201903-0639OC</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-5502-3977</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1073-449X |
| ispartof | American journal of respiratory and critical care medicine, 2020-01, Vol.201 (1), p.95-106 |
| issn | 1073-449X 1535-4970 |
| language | eng |
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| source | MEDLINE; American Thoracic Society (ATS) Journals Online; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Humans Hypertension, Pulmonary - blood Hypertension, Pulmonary - diagnosis Hypertension, Pulmonary - physiopathology Inflammation - blood Inflammation - diagnosis Inflammation - physiopathology Male Models, Animal Positron-Emission Tomography - methods Pulmonary Artery - physiopathology Rats Serum Albumin, Human - analysis |
| title | Assessment of Inflammation in Pulmonary Artery Hypertension by 68 Ga-Mannosylated Human Serum Albumin |
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