{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:25:34Z","timestamp":1793651134795,"version":"4.5.1"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG070042"],"award-info":[{"award-number":["R01AG070042"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Neuroinflammation and cyclooxygenase-2 (COX-2) upregulation are associated with the pathogenesis of degenerative brain diseases such as Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), amyotrophic lateral sclerosis (ALS), epilepsy, and a response to traumatic brain injury (TBI) or stroke. COX-2 is also induced in acute pain, depression, schizophrenia, various cancers, arthritis and in acute allograft rejection. Positron emission tomography (PET) imaging allows for the direct measurement of in vivo COX-2 upregulation and thereby enables disease staging, therapy evaluation and aid quantifying target occupancy of novel nonsteroidal anti-inflammatory drugs or NSAIDs. Thus far, no clinically useful radioligand is established for monitoring COX-2 induction in brain diseases due to the delay in identifying qualified COX-2-selective inhibitors entering the brain. This review examines radiolabeled COX-2 inhibitors reported in the past decade and identifies the most promising radioligands for development as clinically useful PET radioligands. Among the radioligands reported so far, the three tracers that show potential for clinical translation are, [11CTMI], [11C]MC1 and [18F]MTP. These radioligands demonstrated BBB permeablity and in vivo binding to constitutive COX-2 in the brain or induced COX-2 during neuroinflammation.<\/jats:p>","DOI":"10.3390\/molecules26113208","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T11:07:02Z","timestamp":1622113622000},"page":"3208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Progress in PET Imaging of Neuroinflammation Targeting COX-2 Enzyme"],"prefix":"10.3390","volume":"26","author":[{"given":"Jaya","family":"Prabhakaran","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Molotkov","sequence":"additional","affiliation":[{"name":"Department of Radiology, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiva","family":"Mintz","sequence":"additional","affiliation":[{"name":"Department of Radiology, Columbia University Medical Center, New York, NY 10032, USA"},{"name":"Area Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0265-6586","authenticated-orcid":false,"given":"J. John","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA"},{"name":"Area Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"ref_1","first-page":"841","article-title":"Selective Cyclooxygenase-2 Inhibition: Biological and Clinical Effects","volume":"2","author":"Valesini","year":"2000","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev.biochem.69.1.145","article-title":"Cyclooxygenases: Structural, Cellular, and Molecular Biology","volume":"69","author":"Smith","year":"2000","journal-title":"Annu. Rev. 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