{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T03:01:34Z","timestamp":1784775694548,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2024 Lustgarten Foundation-AACR Career Development Award for Pancreatic Cancer Research","award":["24-20-67-LIU"],"award-info":[{"award-number":["24-20-67-LIU"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of Health National Institute of General Medical Sciences CoBRE award","doi-asserted-by":"publisher","award":["P20GM121322"],"award-info":[{"award-number":["P20GM121322"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA273130"],"award-info":[{"award-number":["R01 CA273130"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute Cancer Center","doi-asserted-by":"publisher","award":["P30 CA016672"],"award-info":[{"award-number":["P30 CA016672"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"West Virginia University Cancer Institute Doctoral Dissertation Fellowship"},{"name":"West Virginia University Health Science Center International Fellowship Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Neutrophils, key effector cells of the innate immune system, combat pathogens through mechanisms including the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). While these responses are critical for host defense, prolonged elevation of ROS and dysregulated NETosis mediated by neutrophils have been implicated in autoimmune diseases, chronic inflammation, and cancer. In pancreatic ductal adenocarcinoma (PDAC), a highly aggressive and inflammatory malignancy, an increase in neutrophils infiltrating the tumor microenvironment promotes cancer progression and metastasis through increased ROS production and NET release. Using bioluminescence imaging with the reporter L-012 and NET assays, we assessed ROS and NET release, respectively, induced by phorbol myristate acetate and platelet-activating factor in bone-marrow-isolated neutrophils from wild-type and syngeneic myeloperoxidase (MPO)-deficient mice ex vivo. MPO deficiency impaired both ROS generation and NET release, establishing a positive correlation between these processes. In vivo analyses using subcutaneous and spontaneous murine PDAC models revealed elevated ROS in tumors, which were significantly reduced upon genetic deletion of host MPO or peptidyl arginine deiminase 4, an essential enzyme for NET formation, or after treatment with hydroxychloroquine, a NET inhibitor. Furthermore, luminol and 4-[18F]fluoro-1-naphthol ([18F]4FN), functional L-012 analogs, also enabled non-invasive detection of intratumoral ROS by bioluminescence and PET imaging in vivo, respectively; [18F]4FN PET showed a three-fold increased uptake in PDAC tumors versus muscle. PDAC tissues and blood-isolated neutrophils obtained from PDAC patients exhibited elevated ROS compared to controls ex vivo. Importantly, ROS levels correlated strongly with NET formation in patient samples. These findings reveal a bidirectional relationship between ROS and NETs and highlight the potential utility of L-012- and [18F]4FN-based PET imaging for monitoring NET-associated inflammation in PDAC in vivo.<\/jats:p>","DOI":"10.3390\/antiox14121473","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:17:36Z","timestamp":1765185456000},"page":"1473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Imaging Reactive Oxygen Species with L-012 Reveals Neutrophil Extracellular Trap Formation in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9000-9062","authenticated-orcid":false,"given":"Angisha","family":"Basnet","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn M.","family":"Landreth","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sestito","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, West Virginia University, Morgantown, WV 26506, USA"},{"name":"WVU Cancer Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Ranson","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, West Virginia University, Morgantown, WV 26506, USA"},{"name":"WVU Cancer Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8647-0975","authenticated-orcid":false,"given":"Seth T.","family":"Gammon","sequence":"additional","affiliation":[{"name":"Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center,   Houston, TX 77230, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2120-7217","authenticated-orcid":false,"given":"David","family":"Piwnica-Worms","sequence":"additional","affiliation":[{"name":"Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center,   Houston, TX 77230, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9006-059X","authenticated-orcid":false,"given":"Brian A.","family":"Boone","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, West Virginia University, Morgantown, WV 26506, USA"},{"name":"WVU Cancer Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0671-8390","authenticated-orcid":false,"given":"Tracy W.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV 26506, USA"},{"name":"WVU Cancer Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/j.jaci.2020.02.038","article-title":"The role of neutrophils in host defense and disease","volume":"145","author":"Lehman","year":"2020","journal-title":"J. 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