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PET Imaging of Translocator Protein as a Marker of Malaria-Associated Lung Inflammation
Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a severe complication of malaria that occurs despite effective antimalarial treatment. Currently, noninvasive imaging procedures such as chest X-rays are used to assess edema in established MA-ARDS, but earlier detection methods are...
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Published in: | Infection and immunity 2021-09, Vol.89 (10), p.e0002421-e0002421 |
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creator | Goggi, Julian L Claser, Carla Hartimath, Siddesh V Hor, Pei Xiang Tan, Peng Wen Ramasamy, Boominathan Abdul Rahman, Husaini Cheng, Peter Chang, Zi Wei Nguee, Samantha Yee Teng Tang, Jun Rong Robins, Edward G Renia, Laurent |
description | Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a severe complication of malaria that occurs despite effective antimalarial treatment. Currently, noninvasive imaging procedures such as chest X-rays are used to assess edema in established MA-ARDS, but earlier detection methods are needed to reduce morbidity and mortality. The early stages of MA-ARDS are characterized by the infiltration of leukocytes, in particular monocytes/macrophages; thus, monitoring of immune infiltrates may provide a useful indicator of early pathology. In this study, Plasmodium berghei ANKA-infected C57BL/6 mice, a rodent model of MA-ARDS, were longitudinally imaged using the 18-kDa translocator protein (TSPO) imaging agent [
F]FEPPA as a marker of macrophage accumulation during the development of pathology and in response to combined artesunate and chloroquine diphosphate (ART+CQ) therapy. [
F]FEPPA uptake was compared to blood parasitemia levels and to levels of pulmonary immune cell infiltrates by using flow cytometry. Infected animals showed rapid increases in lung retention of [
F]FEPPA, correlating well with increases in blood parasitemia and pulmonary accumulation of interstitial inflammatory macrophages and major histocompatibility complex class II (MHC-II)-positive alveolar macrophages. Treatment with ART+CQ abrogated this increase in parasitemia and significantly reduced both lung uptake of [
F]FEPPA and levels of macrophage infiltrates. We conclude that retention of [
F]FEPPA in the lungs is well correlated with changes in blood parasitemia and levels of lung-associated macrophages during disease progression and in response to ART+CQ therapy. With further development, TSPO biomarkers may have the potential to accurately assess the early onset of MA-ARDS. |
doi_str_mv | 10.1128/IAI.00024-21 |
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F]FEPPA as a marker of macrophage accumulation during the development of pathology and in response to combined artesunate and chloroquine diphosphate (ART+CQ) therapy. [
F]FEPPA uptake was compared to blood parasitemia levels and to levels of pulmonary immune cell infiltrates by using flow cytometry. Infected animals showed rapid increases in lung retention of [
F]FEPPA, correlating well with increases in blood parasitemia and pulmonary accumulation of interstitial inflammatory macrophages and major histocompatibility complex class II (MHC-II)-positive alveolar macrophages. Treatment with ART+CQ abrogated this increase in parasitemia and significantly reduced both lung uptake of [
F]FEPPA and levels of macrophage infiltrates. We conclude that retention of [
F]FEPPA in the lungs is well correlated with changes in blood parasitemia and levels of lung-associated macrophages during disease progression and in response to ART+CQ therapy. With further development, TSPO biomarkers may have the potential to accurately assess the early onset of MA-ARDS.</description><identifier>ISSN: 0019-9567</identifier><identifier>EISSN: 1098-5522</identifier><identifier>DOI: 10.1128/IAI.00024-21</identifier><identifier>PMID: 34251290</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Animals ; Biomarkers - metabolism ; Disease Models, Animal ; Fungal and Parasitic Infections ; Immunology ; Leukocytes - metabolism ; Lung - metabolism ; Macrophages - metabolism ; Malaria - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes - metabolism ; Plasmodium berghei - pathogenicity ; Pneumonia - metabolism ; Positron-Emission Tomography - methods ; Respiratory Distress Syndrome - metabolism</subject><ispartof>Infection and immunity, 2021-09, Vol.89 (10), p.e0002421-e0002421</ispartof><rights>Copyright © 2021 American Society for Microbiology.</rights><rights>Copyright © 2021 American Society for Microbiology. 2021 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a418t-7326a46c865a0398f90f8b449c97863040d93f7b93f70d940a7c3cdd5eaa6fd23</citedby><cites>FETCH-LOGICAL-a418t-7326a46c865a0398f90f8b449c97863040d93f7b93f70d940a7c3cdd5eaa6fd23</cites><orcidid>0000-0002-3021-3184</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.asm.org/doi/pdf/10.1128/IAI.00024-21$$EPDF$$P50$$Gasm2$$H</linktopdf><linktohtml>$$Uhttps://journals.asm.org/doi/full/10.1128/IAI.00024-21$$EHTML$$P50$$Gasm2$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,3188,27924,27925,52751,52752,52753,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34251290$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Herbert, De’Broski R</contributor><contributor>Herbert, De’Broski R.</contributor><creatorcontrib>Goggi, Julian L</creatorcontrib><creatorcontrib>Claser, Carla</creatorcontrib><creatorcontrib>Hartimath, Siddesh V</creatorcontrib><creatorcontrib>Hor, Pei Xiang</creatorcontrib><creatorcontrib>Tan, Peng Wen</creatorcontrib><creatorcontrib>Ramasamy, Boominathan</creatorcontrib><creatorcontrib>Abdul Rahman, Husaini</creatorcontrib><creatorcontrib>Cheng, Peter</creatorcontrib><creatorcontrib>Chang, Zi Wei</creatorcontrib><creatorcontrib>Nguee, Samantha Yee Teng</creatorcontrib><creatorcontrib>Tang, Jun Rong</creatorcontrib><creatorcontrib>Robins, Edward G</creatorcontrib><creatorcontrib>Renia, Laurent</creatorcontrib><title>PET Imaging of Translocator Protein as a Marker of Malaria-Associated Lung Inflammation</title><title>Infection and immunity</title><addtitle>Infect Immun</addtitle><addtitle>Infect Immun</addtitle><description>Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a severe complication of malaria that occurs despite effective antimalarial treatment. Currently, noninvasive imaging procedures such as chest X-rays are used to assess edema in established MA-ARDS, but earlier detection methods are needed to reduce morbidity and mortality. The early stages of MA-ARDS are characterized by the infiltration of leukocytes, in particular monocytes/macrophages; thus, monitoring of immune infiltrates may provide a useful indicator of early pathology. In this study, Plasmodium berghei ANKA-infected C57BL/6 mice, a rodent model of MA-ARDS, were longitudinally imaged using the 18-kDa translocator protein (TSPO) imaging agent [
F]FEPPA as a marker of macrophage accumulation during the development of pathology and in response to combined artesunate and chloroquine diphosphate (ART+CQ) therapy. [
F]FEPPA uptake was compared to blood parasitemia levels and to levels of pulmonary immune cell infiltrates by using flow cytometry. Infected animals showed rapid increases in lung retention of [
F]FEPPA, correlating well with increases in blood parasitemia and pulmonary accumulation of interstitial inflammatory macrophages and major histocompatibility complex class II (MHC-II)-positive alveolar macrophages. Treatment with ART+CQ abrogated this increase in parasitemia and significantly reduced both lung uptake of [
F]FEPPA and levels of macrophage infiltrates. We conclude that retention of [
F]FEPPA in the lungs is well correlated with changes in blood parasitemia and levels of lung-associated macrophages during disease progression and in response to ART+CQ therapy. With further development, TSPO biomarkers may have the potential to accurately assess the early onset of MA-ARDS.</description><subject>Animals</subject><subject>Biomarkers - metabolism</subject><subject>Disease Models, Animal</subject><subject>Fungal and Parasitic Infections</subject><subject>Immunology</subject><subject>Leukocytes - metabolism</subject><subject>Lung - metabolism</subject><subject>Macrophages - metabolism</subject><subject>Malaria - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Monocytes - metabolism</subject><subject>Plasmodium berghei - pathogenicity</subject><subject>Pneumonia - metabolism</subject><subject>Positron-Emission Tomography - methods</subject><subject>Respiratory Distress Syndrome - metabolism</subject><issn>0019-9567</issn><issn>1098-5522</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp1kU1P3DAQhi1UBMuWG-cqxyIR6s_EvlRaIT4i7QoOW3G0Zh1nMU3srZ1U6r8n210QHLh4PJpn3tHMi9AZwZeEUPmjmlWXGGPKc0oO0IRgJXMhKP2CJhgTlStRlMfoJKXnMeWcyyN0zDgVhCo8QY8P18us6mDt_DoLTbaM4FMbDPQhZg8x9Nb5DFIG2QLibxu3zAJaiA7yWUrBOOhtnc2Hsb3yTQtdB70L_is6bKBN9nQfp-jXzfXy6i6f399WV7N5DpzIPi8ZLYAXRhYCMFOyUbiRK86VUaUsGOa4VqwpV9tn_HIMpWGmroUFKJqasin6udPdDKvO1sb6PkKrN9F1EP_pAE5_rHj3pNfhr5acC1KyUeD7XiCGP4NNve5cMrZtwdswJE2FwAWVlG9nXexQE0NK0TZvYwjWWy_06IX-74WmZMTPdzikjurnMEQ_XuIz9tv7Nd6EX41iL6kGkNc</recordid><startdate>20210916</startdate><enddate>20210916</enddate><creator>Goggi, Julian L</creator><creator>Claser, Carla</creator><creator>Hartimath, Siddesh V</creator><creator>Hor, Pei Xiang</creator><creator>Tan, Peng Wen</creator><creator>Ramasamy, Boominathan</creator><creator>Abdul Rahman, Husaini</creator><creator>Cheng, Peter</creator><creator>Chang, Zi Wei</creator><creator>Nguee, Samantha Yee Teng</creator><creator>Tang, Jun Rong</creator><creator>Robins, Edward G</creator><creator>Renia, Laurent</creator><general>American Society for Microbiology</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/0000-0002-3021-3184</orcidid></search><sort><creationdate>20210916</creationdate><title>PET Imaging of Translocator Protein as a Marker of Malaria-Associated Lung Inflammation</title><author>Goggi, Julian L ; Claser, Carla ; Hartimath, Siddesh V ; Hor, Pei Xiang ; Tan, Peng Wen ; Ramasamy, Boominathan ; Abdul Rahman, Husaini ; Cheng, Peter ; Chang, Zi Wei ; Nguee, Samantha Yee Teng ; Tang, Jun Rong ; Robins, Edward G ; Renia, Laurent</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a418t-7326a46c865a0398f90f8b449c97863040d93f7b93f70d940a7c3cdd5eaa6fd23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Biomarkers - metabolism</topic><topic>Disease Models, Animal</topic><topic>Fungal and Parasitic Infections</topic><topic>Immunology</topic><topic>Leukocytes - metabolism</topic><topic>Lung - metabolism</topic><topic>Macrophages - metabolism</topic><topic>Malaria - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Monocytes - metabolism</topic><topic>Plasmodium berghei - pathogenicity</topic><topic>Pneumonia - metabolism</topic><topic>Positron-Emission Tomography - methods</topic><topic>Respiratory Distress Syndrome - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goggi, Julian L</creatorcontrib><creatorcontrib>Claser, Carla</creatorcontrib><creatorcontrib>Hartimath, Siddesh V</creatorcontrib><creatorcontrib>Hor, Pei Xiang</creatorcontrib><creatorcontrib>Tan, Peng Wen</creatorcontrib><creatorcontrib>Ramasamy, Boominathan</creatorcontrib><creatorcontrib>Abdul Rahman, Husaini</creatorcontrib><creatorcontrib>Cheng, Peter</creatorcontrib><creatorcontrib>Chang, Zi Wei</creatorcontrib><creatorcontrib>Nguee, Samantha Yee Teng</creatorcontrib><creatorcontrib>Tang, Jun Rong</creatorcontrib><creatorcontrib>Robins, Edward G</creatorcontrib><creatorcontrib>Renia, Laurent</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>Infection and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goggi, Julian L</au><au>Claser, Carla</au><au>Hartimath, Siddesh V</au><au>Hor, Pei Xiang</au><au>Tan, Peng Wen</au><au>Ramasamy, Boominathan</au><au>Abdul Rahman, Husaini</au><au>Cheng, Peter</au><au>Chang, Zi Wei</au><au>Nguee, Samantha Yee Teng</au><au>Tang, Jun Rong</au><au>Robins, Edward G</au><au>Renia, Laurent</au><au>Herbert, De’Broski R</au><au>Herbert, De’Broski R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PET Imaging of Translocator Protein as a Marker of Malaria-Associated Lung Inflammation</atitle><jtitle>Infection and immunity</jtitle><stitle>Infect Immun</stitle><addtitle>Infect Immun</addtitle><date>2021-09-16</date><risdate>2021</risdate><volume>89</volume><issue>10</issue><spage>e0002421</spage><epage>e0002421</epage><pages>e0002421-e0002421</pages><issn>0019-9567</issn><eissn>1098-5522</eissn><abstract>Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a severe complication of malaria that occurs despite effective antimalarial treatment. Currently, noninvasive imaging procedures such as chest X-rays are used to assess edema in established MA-ARDS, but earlier detection methods are needed to reduce morbidity and mortality. The early stages of MA-ARDS are characterized by the infiltration of leukocytes, in particular monocytes/macrophages; thus, monitoring of immune infiltrates may provide a useful indicator of early pathology. In this study, Plasmodium berghei ANKA-infected C57BL/6 mice, a rodent model of MA-ARDS, were longitudinally imaged using the 18-kDa translocator protein (TSPO) imaging agent [
F]FEPPA as a marker of macrophage accumulation during the development of pathology and in response to combined artesunate and chloroquine diphosphate (ART+CQ) therapy. [
F]FEPPA uptake was compared to blood parasitemia levels and to levels of pulmonary immune cell infiltrates by using flow cytometry. Infected animals showed rapid increases in lung retention of [
F]FEPPA, correlating well with increases in blood parasitemia and pulmonary accumulation of interstitial inflammatory macrophages and major histocompatibility complex class II (MHC-II)-positive alveolar macrophages. Treatment with ART+CQ abrogated this increase in parasitemia and significantly reduced both lung uptake of [
F]FEPPA and levels of macrophage infiltrates. We conclude that retention of [
F]FEPPA in the lungs is well correlated with changes in blood parasitemia and levels of lung-associated macrophages during disease progression and in response to ART+CQ therapy. With further development, TSPO biomarkers may have the potential to accurately assess the early onset of MA-ARDS.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>34251290</pmid><doi>10.1128/IAI.00024-21</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3021-3184</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biomarkers - metabolism Disease Models, Animal Fungal and Parasitic Infections Immunology Leukocytes - metabolism Lung - metabolism Macrophages - metabolism Malaria - metabolism Male Mice Mice, Inbred C57BL Monocytes - metabolism Plasmodium berghei - pathogenicity Pneumonia - metabolism Positron-Emission Tomography - methods Respiratory Distress Syndrome - metabolism |
title | PET Imaging of Translocator Protein as a Marker of Malaria-Associated Lung Inflammation |
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