Heterogeneity in Lung 18FDG Uptake in Pulmonary Arterial Hypertension: Potential of Dynamic 18FDG Positron Emission Tomography With Kinetic Analysis as a Bridging Biomarker for Pulmonary Vascular Remodeling Targeted Treatments

BACKGROUND—Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, under...

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Published in:Circulation (New York, N.Y.) N.Y.), 2013-09, Vol.128 (11), p.1214-1224
Main Authors: Zhao, Lan, Ashek, Ali, Wang, Lei, Fang, Wei, Dabral, Swati, Dubois, Olivier, Cupitt, John, Pullamsetti, Soni Savai, Cotroneo, Emanuele, Jones, Hazel, Tomasi, Gianpaolo, Nguyen, Quang-De, Aboagye, Eric O., El-Bahrawy, Mona A., Barnes, Gareth, Howard, Luke S., Gibbs, J. Simon R., Gsell, Willy, He, Jian-Guo, Wilkins, Martin R.
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Language:English
Subjects:
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Medical sciences
Pneumology
Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases
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container_issue 11
container_start_page 1214
container_title Circulation (New York, N.Y.)
container_volume 128
creator Zhao, Lan
Ashek, Ali
Wang, Lei
Fang, Wei
Dabral, Swati
Dubois, Olivier
Cupitt, John
Pullamsetti, Soni Savai
Cotroneo, Emanuele
Jones, Hazel
Tomasi, Gianpaolo
Nguyen, Quang-De
Aboagye, Eric O.
El-Bahrawy, Mona A.
Barnes, Gareth
Howard, Luke S.
Gibbs, J. Simon R.
Gsell, Willy
He, Jian-Guo
Wilkins, Martin R.
description BACKGROUND—Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH. METHODS AND RESULTS—Dynamic positron emission tomography imaging with fluorine-18–labeled 2-fluoro-2-deoxyglucose (FDG) ligand with kinetic analysis demonstrated increased mean lung parenchymal uptake in 20 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score3.27±1.22), and 2 patients with connective tissue disease (5.07 and 7.11) compared with controls (2.02±0.71; P
doi_str_mv 10.1161/CIRCULATIONAHA.113.004136
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Simon R. ; Gsell, Willy ; He, Jian-Guo ; Wilkins, Martin R.</creator><creatorcontrib>Zhao, Lan ; Ashek, Ali ; Wang, Lei ; Fang, Wei ; Dabral, Swati ; Dubois, Olivier ; Cupitt, John ; Pullamsetti, Soni Savai ; Cotroneo, Emanuele ; Jones, Hazel ; Tomasi, Gianpaolo ; Nguyen, Quang-De ; Aboagye, Eric O. ; El-Bahrawy, Mona A. ; Barnes, Gareth ; Howard, Luke S. ; Gibbs, J. Simon R. ; Gsell, Willy ; He, Jian-Guo ; Wilkins, Martin R.</creatorcontrib><description>BACKGROUND—Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH. METHODS AND RESULTS—Dynamic positron emission tomography imaging with fluorine-18–labeled 2-fluoro-2-deoxyglucose (FDG) ligand with kinetic analysis demonstrated increased mean lung parenchymal uptake in 20 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score3.27±1.22), and 2 patients with connective tissue disease (5.07 and 7.11) compared with controls (2.02±0.71; P&lt;0.05). Further compartment analysis confirmed increased lung glucose metabolism in IPAH. Lung FDG uptake and metabolism varied within the IPAH population and within the lungs of individual patients, consistent with the recognized heterogeneity of vascular pathology in this disease. The monocrotaline rat PAH model also showed increased lung FDG uptake, which was reduced along with improvements in vascular pathology after treatment with dicholoroacetate and 2 tyrosine kinase inhibitors, imatinib and sunitinib. Hyperproliferative pulmonary vascular fibroblasts isolated from IPAH patients exhibited upregulated glycolytic gene expression, along with increased cellular FDG uptake; both were reduced by dicholoroacetate and imatinib. CONCLUSIONS—Some patients with IPAH exhibit increased lung FDG uptake. FDG positron emission tomography imaging is a tool to investigate the molecular pathology of PAH and its response to treatment.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.113.004136</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: by the American College of Cardiology Foundation and the American Heart Association, Inc</publisher><subject>Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Medical sciences ; Pneumology ; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases</subject><ispartof>Circulation (New York, N.Y.), 2013-09, Vol.128 (11), p.1214-1224</ispartof><rights>2013 by the American College of Cardiology Foundation and the American Heart Association, Inc.</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=27712080$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Lan</creatorcontrib><creatorcontrib>Ashek, Ali</creatorcontrib><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Fang, Wei</creatorcontrib><creatorcontrib>Dabral, Swati</creatorcontrib><creatorcontrib>Dubois, Olivier</creatorcontrib><creatorcontrib>Cupitt, John</creatorcontrib><creatorcontrib>Pullamsetti, Soni Savai</creatorcontrib><creatorcontrib>Cotroneo, Emanuele</creatorcontrib><creatorcontrib>Jones, Hazel</creatorcontrib><creatorcontrib>Tomasi, Gianpaolo</creatorcontrib><creatorcontrib>Nguyen, Quang-De</creatorcontrib><creatorcontrib>Aboagye, Eric O.</creatorcontrib><creatorcontrib>El-Bahrawy, Mona A.</creatorcontrib><creatorcontrib>Barnes, Gareth</creatorcontrib><creatorcontrib>Howard, Luke S.</creatorcontrib><creatorcontrib>Gibbs, J. Simon R.</creatorcontrib><creatorcontrib>Gsell, Willy</creatorcontrib><creatorcontrib>He, Jian-Guo</creatorcontrib><creatorcontrib>Wilkins, Martin R.</creatorcontrib><title>Heterogeneity in Lung 18FDG Uptake in Pulmonary Arterial Hypertension: Potential of Dynamic 18FDG Positron Emission Tomography With Kinetic Analysis as a Bridging Biomarker for Pulmonary Vascular Remodeling Targeted Treatments</title><title>Circulation (New York, N.Y.)</title><description>BACKGROUND—Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH. METHODS AND RESULTS—Dynamic positron emission tomography imaging with fluorine-18–labeled 2-fluoro-2-deoxyglucose (FDG) ligand with kinetic analysis demonstrated increased mean lung parenchymal uptake in 20 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score3.27±1.22), and 2 patients with connective tissue disease (5.07 and 7.11) compared with controls (2.02±0.71; P&lt;0.05). Further compartment analysis confirmed increased lung glucose metabolism in IPAH. Lung FDG uptake and metabolism varied within the IPAH population and within the lungs of individual patients, consistent with the recognized heterogeneity of vascular pathology in this disease. The monocrotaline rat PAH model also showed increased lung FDG uptake, which was reduced along with improvements in vascular pathology after treatment with dicholoroacetate and 2 tyrosine kinase inhibitors, imatinib and sunitinib. Hyperproliferative pulmonary vascular fibroblasts isolated from IPAH patients exhibited upregulated glycolytic gene expression, along with increased cellular FDG uptake; both were reduced by dicholoroacetate and imatinib. CONCLUSIONS—Some patients with IPAH exhibit increased lung FDG uptake. FDG positron emission tomography imaging is a tool to investigate the molecular pathology of PAH and its response to treatment.</description><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Medical sciences</subject><subject>Pneumology</subject><subject>Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. 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Simon R.</au><au>Gsell, Willy</au><au>He, Jian-Guo</au><au>Wilkins, Martin R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heterogeneity in Lung 18FDG Uptake in Pulmonary Arterial Hypertension: Potential of Dynamic 18FDG Positron Emission Tomography With Kinetic Analysis as a Bridging Biomarker for Pulmonary Vascular Remodeling Targeted Treatments</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><date>2013-09-10</date><risdate>2013</risdate><volume>128</volume><issue>11</issue><spage>1214</spage><epage>1224</epage><pages>1214-1224</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>BACKGROUND—Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH. METHODS AND RESULTS—Dynamic positron emission tomography imaging with fluorine-18–labeled 2-fluoro-2-deoxyglucose (FDG) ligand with kinetic analysis demonstrated increased mean lung parenchymal uptake in 20 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score3.27±1.22), and 2 patients with connective tissue disease (5.07 and 7.11) compared with controls (2.02±0.71; P&lt;0.05). Further compartment analysis confirmed increased lung glucose metabolism in IPAH. Lung FDG uptake and metabolism varied within the IPAH population and within the lungs of individual patients, consistent with the recognized heterogeneity of vascular pathology in this disease. The monocrotaline rat PAH model also showed increased lung FDG uptake, which was reduced along with improvements in vascular pathology after treatment with dicholoroacetate and 2 tyrosine kinase inhibitors, imatinib and sunitinib. Hyperproliferative pulmonary vascular fibroblasts isolated from IPAH patients exhibited upregulated glycolytic gene expression, along with increased cellular FDG uptake; both were reduced by dicholoroacetate and imatinib. CONCLUSIONS—Some patients with IPAH exhibit increased lung FDG uptake. FDG positron emission tomography imaging is a tool to investigate the molecular pathology of PAH and its response to treatment.</abstract><cop>Hagerstown, MD</cop><pub>by the American College of Cardiology Foundation and the American Heart Association, Inc</pub><doi>10.1161/CIRCULATIONAHA.113.004136</doi><tpages>11</tpages></addata></record>
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source EZB Electronic Journals Library
subjects Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Medical sciences
Pneumology
Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases
title Heterogeneity in Lung 18FDG Uptake in Pulmonary Arterial Hypertension: Potential of Dynamic 18FDG Positron Emission Tomography With Kinetic Analysis as a Bridging Biomarker for Pulmonary Vascular Remodeling Targeted Treatments
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