[18F]Fluorodeoxyglucose Positron Emission Tomography for Lung Antiinflammatory Response Evaluation
Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic...
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| Veröffentlicht in: | American journal of respiratory and critical care medicine 2009-09, Vol.180 (6), p.533-539 |
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| creator | Chen, Delphine L Bedient, Timothy J Kozlowski, James Rosenbluth, Daniel B Isakow, Warren Ferkol, Thomas W Thomas, Betsy Mintun, Mark A Schuster, Daniel P Walter, Michael J |
| description | Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation.
To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentally-induced lung inflammation.
Eighteen healthy volunteers were randomized to receive placebo, lovastatin, or rhAPC before intrabronchial segmental endotoxin challenge. FDG-PET imaging was performed before and after endotoxin instillation. The rate of [(18)F]FDG uptake was calculated as the influx constant K(i) by Patlak graphical analysis. Bronchoalveolar lavage (BAL) was performed to determine leukocyte concentrations for correlation with the PET imaging results.
There was a statistically significant decrease in K(i) in the lovastatin-treated group that was not seen in the placebo-treated group, suggesting attenuation of inflammation by lovastatin treatment despite a small decrease in BAL total leukocyte and neutrophil counts that was not statistically significant. No significant decrease in K(i) was observed in the rhAPC-treated group, correlating with a lack of change in BAL parameters and indicating no significant antiinflammatory effect with rhAPC.
FDG-PET imaging is a sensitive method for quantifying the lung-specific response to antiinflammatory therapies and may serve as an attractive platform for assessing the efficacy of novel antiinflammatory therapies at early phases in the drug development process. Clinical trial registered with www.clinicaltrials.gov (NCT00741013). |
| doi_str_mv | 10.1164/rccm.200904-0501OC |
| format | Article |
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To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentally-induced lung inflammation.
Eighteen healthy volunteers were randomized to receive placebo, lovastatin, or rhAPC before intrabronchial segmental endotoxin challenge. FDG-PET imaging was performed before and after endotoxin instillation. The rate of [(18)F]FDG uptake was calculated as the influx constant K(i) by Patlak graphical analysis. Bronchoalveolar lavage (BAL) was performed to determine leukocyte concentrations for correlation with the PET imaging results.
There was a statistically significant decrease in K(i) in the lovastatin-treated group that was not seen in the placebo-treated group, suggesting attenuation of inflammation by lovastatin treatment despite a small decrease in BAL total leukocyte and neutrophil counts that was not statistically significant. No significant decrease in K(i) was observed in the rhAPC-treated group, correlating with a lack of change in BAL parameters and indicating no significant antiinflammatory effect with rhAPC.
FDG-PET imaging is a sensitive method for quantifying the lung-specific response to antiinflammatory therapies and may serve as an attractive platform for assessing the efficacy of novel antiinflammatory therapies at early phases in the drug development process. Clinical trial registered with www.clinicaltrials.gov (NCT00741013).</description><identifier>ISSN: 1073-449X</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/rccm.200904-0501OC</identifier><identifier>PMID: 19574441</identifier><language>eng</language><publisher>New York, NY: Am Thoracic Soc</publisher><subject>Adult ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Anticholesteremic Agents - therapeutic use ; Biological and medical sciences ; Biomarkers ; Bronchoalveolar Lavage Fluid ; C. Critical Care ; Cystic fibrosis ; Double-Blind Method ; Female ; Fluorodeoxyglucose F18 ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Inflammation ; Intensive care medicine ; Investigative techniques, diagnostic techniques (general aspects) ; Lavage ; Leukocytes ; Lovastatin - therapeutic use ; Male ; Medical sciences ; Neutrophil Activation ; Neutrophils ; Pneumonia - diagnostic imaging ; Pneumonia - drug therapy ; Pneumonia - immunology ; Positron-Emission Tomography - methods ; Protein C - therapeutic use ; Radiodiagnosis. Nmr imagery. Nmr spectrometry ; Radiopharmaceuticals ; Recombinant Proteins - therapeutic use ; Respiratory system ; Tomography ; Young Adult</subject><ispartof>American journal of respiratory and critical care medicine, 2009-09, Vol.180 (6), p.533-539</ispartof><rights>2009 INIST-CNRS</rights><rights>Copyright American Thoracic Society Sep 15, 2009</rights><rights>Copyright © 2009, American Thoracic Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-f9f7feb9cc2339b187cc1afbc497d6e33ffcf2795e3845d4badee767a86be02d3</citedby><cites>FETCH-LOGICAL-c557t-f9f7feb9cc2339b187cc1afbc497d6e33ffcf2795e3845d4badee767a86be02d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,4025,4026,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21959512$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19574441$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Delphine L</creatorcontrib><creatorcontrib>Bedient, Timothy J</creatorcontrib><creatorcontrib>Kozlowski, James</creatorcontrib><creatorcontrib>Rosenbluth, Daniel B</creatorcontrib><creatorcontrib>Isakow, Warren</creatorcontrib><creatorcontrib>Ferkol, Thomas W</creatorcontrib><creatorcontrib>Thomas, Betsy</creatorcontrib><creatorcontrib>Mintun, Mark A</creatorcontrib><creatorcontrib>Schuster, Daniel P</creatorcontrib><creatorcontrib>Walter, Michael J</creatorcontrib><title>[18F]Fluorodeoxyglucose Positron Emission Tomography for Lung Antiinflammatory Response Evaluation</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation.
To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentally-induced lung inflammation.
Eighteen healthy volunteers were randomized to receive placebo, lovastatin, or rhAPC before intrabronchial segmental endotoxin challenge. FDG-PET imaging was performed before and after endotoxin instillation. The rate of [(18)F]FDG uptake was calculated as the influx constant K(i) by Patlak graphical analysis. Bronchoalveolar lavage (BAL) was performed to determine leukocyte concentrations for correlation with the PET imaging results.
There was a statistically significant decrease in K(i) in the lovastatin-treated group that was not seen in the placebo-treated group, suggesting attenuation of inflammation by lovastatin treatment despite a small decrease in BAL total leukocyte and neutrophil counts that was not statistically significant. No significant decrease in K(i) was observed in the rhAPC-treated group, correlating with a lack of change in BAL parameters and indicating no significant antiinflammatory effect with rhAPC.
FDG-PET imaging is a sensitive method for quantifying the lung-specific response to antiinflammatory therapies and may serve as an attractive platform for assessing the efficacy of novel antiinflammatory therapies at early phases in the drug development process. Clinical trial registered with www.clinicaltrials.gov (NCT00741013).</description><subject>Adult</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Anticholesteremic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Bronchoalveolar Lavage Fluid</subject><subject>C. Critical Care</subject><subject>Cystic fibrosis</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Fluorodeoxyglucose F18</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Inflammation</subject><subject>Intensive care medicine</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Lavage</subject><subject>Leukocytes</subject><subject>Lovastatin - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neutrophil Activation</subject><subject>Neutrophils</subject><subject>Pneumonia - diagnostic imaging</subject><subject>Pneumonia - drug therapy</subject><subject>Pneumonia - immunology</subject><subject>Positron-Emission Tomography - methods</subject><subject>Protein C - therapeutic use</subject><subject>Radiodiagnosis. Nmr imagery. Nmr spectrometry</subject><subject>Radiopharmaceuticals</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Respiratory system</subject><subject>Tomography</subject><subject>Young Adult</subject><issn>1073-449X</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpdkWGLFCEcxiU6umvrC_QihqCgF3PpqOP4JjiW3TpYuIgLgghxHJ11cXTTmav99rnMcnUHgn_w9zz6-ADwCsFLhGryISo1XFYQckhKSCG6WT4BF4hiWhLO4NM8Q4ZLQvj3c_A8pR2EqGoQfAbOEaeMEIIuQPsDNeufazeFGDod_hx6N6mQdPElJDvG4IvVYFOyebgNQ-ij3G8PhQmx2Ey-L678aK03Tg6DHEM8FF912gef9as76SY5ZuELcGakS_rlaV-Ab-vV7fJzubn5dL282pSKUjaWhhtmdMuVqjDmLWqYUkiaVuUwXa0xNkaZinGqcUNoR1rZac1qJpu61bDq8AJ8nH33UzvoTmk_RunEPtpBxoMI0oqHJ95uRR_uRMVIXiQbvDsZxPBr0mkUObrSzkmvw5REzWpMIa8z-OYRuAtT9DmcQJzXhJH88QtQzZCKIaWozf1LEBTH_sSxPzH3J-b-suj1_xn-SU6FZeDtCZBJSWei9Mqme67KIKeoytz7mdvafvvbRi3SIJ3LtkjI3fFm1EBRC4ox_guy2Lar</recordid><startdate>20090915</startdate><enddate>20090915</enddate><creator>Chen, Delphine L</creator><creator>Bedient, Timothy J</creator><creator>Kozlowski, James</creator><creator>Rosenbluth, Daniel B</creator><creator>Isakow, Warren</creator><creator>Ferkol, Thomas W</creator><creator>Thomas, Betsy</creator><creator>Mintun, Mark A</creator><creator>Schuster, Daniel P</creator><creator>Walter, Michael J</creator><general>Am Thoracic Soc</general><general>American Thoracic Society</general><scope>IQODW</scope><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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090915</creationdate><title>[18F]Fluorodeoxyglucose Positron Emission Tomography for Lung Antiinflammatory Response Evaluation</title><author>Chen, Delphine L ; Bedient, Timothy J ; Kozlowski, James ; Rosenbluth, Daniel B ; Isakow, Warren ; Ferkol, Thomas W ; Thomas, Betsy ; Mintun, Mark A ; Schuster, Daniel P ; Walter, Michael J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-f9f7feb9cc2339b187cc1afbc497d6e33ffcf2795e3845d4badee767a86be02d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Anticholesteremic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Bronchoalveolar Lavage Fluid</topic><topic>C. Critical Care</topic><topic>Cystic fibrosis</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Fluorodeoxyglucose F18</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Inflammation</topic><topic>Intensive care medicine</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Lavage</topic><topic>Leukocytes</topic><topic>Lovastatin - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neutrophil Activation</topic><topic>Neutrophils</topic><topic>Pneumonia - diagnostic imaging</topic><topic>Pneumonia - drug therapy</topic><topic>Pneumonia - immunology</topic><topic>Positron-Emission Tomography - methods</topic><topic>Protein C - therapeutic use</topic><topic>Radiodiagnosis. Nmr imagery. Nmr spectrometry</topic><topic>Radiopharmaceuticals</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>Respiratory system</topic><topic>Tomography</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Delphine L</creatorcontrib><creatorcontrib>Bedient, Timothy J</creatorcontrib><creatorcontrib>Kozlowski, James</creatorcontrib><creatorcontrib>Rosenbluth, Daniel B</creatorcontrib><creatorcontrib>Isakow, Warren</creatorcontrib><creatorcontrib>Ferkol, Thomas W</creatorcontrib><creatorcontrib>Thomas, Betsy</creatorcontrib><creatorcontrib>Mintun, Mark A</creatorcontrib><creatorcontrib>Schuster, Daniel P</creatorcontrib><creatorcontrib>Walter, Michael J</creatorcontrib><collection>Pascal-Francis</collection><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>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Delphine L</au><au>Bedient, Timothy J</au><au>Kozlowski, James</au><au>Rosenbluth, Daniel B</au><au>Isakow, Warren</au><au>Ferkol, Thomas W</au><au>Thomas, Betsy</au><au>Mintun, Mark A</au><au>Schuster, Daniel P</au><au>Walter, Michael J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>[18F]Fluorodeoxyglucose Positron Emission Tomography for Lung Antiinflammatory Response Evaluation</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><addtitle>Am J Respir Crit Care Med</addtitle><date>2009-09-15</date><risdate>2009</risdate><volume>180</volume><issue>6</issue><spage>533</spage><epage>539</epage><pages>533-539</pages><issn>1073-449X</issn><eissn>1535-4970</eissn><abstract>Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation.
To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentally-induced lung inflammation.
Eighteen healthy volunteers were randomized to receive placebo, lovastatin, or rhAPC before intrabronchial segmental endotoxin challenge. FDG-PET imaging was performed before and after endotoxin instillation. The rate of [(18)F]FDG uptake was calculated as the influx constant K(i) by Patlak graphical analysis. Bronchoalveolar lavage (BAL) was performed to determine leukocyte concentrations for correlation with the PET imaging results.
There was a statistically significant decrease in K(i) in the lovastatin-treated group that was not seen in the placebo-treated group, suggesting attenuation of inflammation by lovastatin treatment despite a small decrease in BAL total leukocyte and neutrophil counts that was not statistically significant. No significant decrease in K(i) was observed in the rhAPC-treated group, correlating with a lack of change in BAL parameters and indicating no significant antiinflammatory effect with rhAPC.
FDG-PET imaging is a sensitive method for quantifying the lung-specific response to antiinflammatory therapies and may serve as an attractive platform for assessing the efficacy of novel antiinflammatory therapies at early phases in the drug development process. Clinical trial registered with www.clinicaltrials.gov (NCT00741013).</abstract><cop>New York, NY</cop><pub>Am Thoracic Soc</pub><pmid>19574441</pmid><doi>10.1164/rccm.200904-0501OC</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1073-449X |
| ispartof | American journal of respiratory and critical care medicine, 2009-09, Vol.180 (6), p.533-539 |
| issn | 1073-449X 1535-4970 |
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| source | MEDLINE; Journals@Ovid Complete; American Thoracic Society (ATS) Journals Online; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Anticholesteremic Agents - therapeutic use Biological and medical sciences Biomarkers Bronchoalveolar Lavage Fluid C. Critical Care Cystic fibrosis Double-Blind Method Female Fluorodeoxyglucose F18 Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Inflammation Intensive care medicine Investigative techniques, diagnostic techniques (general aspects) Lavage Leukocytes Lovastatin - therapeutic use Male Medical sciences Neutrophil Activation Neutrophils Pneumonia - diagnostic imaging Pneumonia - drug therapy Pneumonia - immunology Positron-Emission Tomography - methods Protein C - therapeutic use Radiodiagnosis. Nmr imagery. Nmr spectrometry Radiopharmaceuticals Recombinant Proteins - therapeutic use Respiratory system Tomography Young Adult |
| title | [18F]Fluorodeoxyglucose Positron Emission Tomography for Lung Antiinflammatory Response Evaluation |
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