{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:13:31Z","timestamp":1788344011569,"version":"build-2803163510"},"reference-count":35,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2015,7,8]],"date-time":"2015-07-08T00:00:00Z","timestamp":1436313600000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,11,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fatty acid amide hydrolase (FAAH) regulates endocannabinoid signaling. [11C]CURB, an irreversibly binding FAAH inhibitor, has been developed for clinical research imaging with PET. However, no fluorine-18 labeled radiotracer for FAAH has yet advanced to human studies. [18F]DOPP ([18F]3-(4,5-dihydrooxazol-2-yl)phenyl (5-fluoropentyl)carbamate) has been identified as a promising 18F-labeled analogue based on rodent studies. The goal of this work is to evaluate [18F]DOPP in nonhuman primates to support its clinical translation. High specific activity [18F]DOPP (5\u20136 Ci\u00b7\u03bcmol\u20131) was administered intravenously (iv) to three baboons (2M\/1F, 3\u20134 years old). The distribution and pharmacokinetics were quantified following a 2 h dynamic imaging session using a simultaneous PET\/MR scanner. Pretreatment with the FAAH-selective inhibitor, URB597, was carried out at 200 or 300 \u03bcg\/kg iv, 10 min prior to [18F]DOPP administration. Rapid arterial blood sampling for the first 3 min was followed by interval sampling with metabolite analysis to provide a parent radiotracer plasma input function that indicated \u223c95% baseline metabolism at 60 min and a reduced rate of metabolism after pretreatment with URB597. Regional distribution data were analyzed with 1-, 2-, and 3-tissue compartment models (TCMs), with and without irreversible trapping since [18F]DOPP covalently links to the active site of FAAH. Consistent with previous findings for [11C]CURB, the 2TCM with irreversible binding was found to provide the best fit for modeling the data in all regions. The composite parameter \u03bbk3 was therefore used to evaluate whole brain (WB) and regional binding of [18F]DOPP. Pretreatment studies showed inhibition of \u03bbk3 across all brain regions (WB baseline: 0.112 mL\/cm3\/min; 300 \u03bcg\/kg URB597: 0.058 mL\/cm3\/min), suggesting that [18F]DOPP binding is specific for FAAH, consistent with previous rodent data.<\/jats:p>","DOI":"10.1021\/mp500316h","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T12:06:48Z","timestamp":1404821208000},"page":"3832-3838","source":"Crossref","is-referenced-by-count":20,"title":["PET Imaging of Fatty Acid Amide Hydrolase with [18F]DOPP in Nonhuman Primates"],"prefix":"10.1021","volume":"11","author":[{"given":"Benjamin H.","family":"Rotstein","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital , , , ,","place":["Boston, Massachusetts, United States, 02114"]},{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02114"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Ying","family":"Wey","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02114"]},{"name":"Massachusetts General Hospital , , , ,","place":["Charlestown, Massachusetts, United States, 02129"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"Shoup","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital , , , ,","place":["Boston, Massachusetts, United States, 02114"]},{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02114"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan A.","family":"Wilson","sequence":"additional","affiliation":[{"name":"University of Toronto , , , ,","place":["Toronto, Ontario, Canada, M5T 1R8"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H.","family":"Liang","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital , , , ,","place":["Boston, Massachusetts, United States, 02114"]},{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02114"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Hooker","sequence":"additional","affiliation":[{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02114"]},{"name":"Massachusetts General Hospital , , , ,","place":["Charlestown, Massachusetts, United States, 02129"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Vasdev","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital , , , ,","place":["Boston, Massachusetts, United States, 02114"]},{"name":"Harvard Medical School , , , ,","place":["Boston, Massachusetts, United States, 02114"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,7,8]]},"reference":[{"key":"2026090205180773800_cit1","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/nrn1247","article-title":"The Molecular\nLogic of Endocannabinoid Signalling","volume":"4","author":"Piomelli","year":"2003","journal-title":"Nat. Rev.\nNeurosci."},{"key":"2026090205180773800_cit2","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1021\/cr0782067","article-title":"Enzymatic\nPathways That Regulate\nEndocannabinoid Signaling in the Nervous System","volume":"108","author":"Ahn","year":"2008","journal-title":"Chem. Rev."},{"key":"2026090205180773800_cit3","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.tins.2011.03.003","article-title":"Supply and Demand for\nEndocannabinoids","volume":"34","author":"Alger","year":"2011","journal-title":"Trends\nNeurosci."},{"key":"2026090205180773800_cit4","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1472-8206.2006.00442.x","article-title":"The Cannabinoid\nSystem and Its Pharmacological Manipulation \u2013 a Review, with\nEmphasis upon the Uptake and Hydrolysis of Anandamide","volume":"20","author":"Fowler","year":"2006","journal-title":"Fundam. Clin. Pharmacol."},{"key":"2026090205180773800_cit5","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.tips.2012.01.001","article-title":"Anandamide\nUptake Explained?","volume":"33","author":"Fowler","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"2026090205180773800_cit6","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nrd2553","article-title":"Targeting the Endocannabinoid System: To Enhance or Reduce?","volume":"7","author":"Di Marzo","year":"2008","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026090205180773800_cit7","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1124\/pr.112.006387","article-title":"Chemical Probes of Endocannabinoid Metabolism","volume":"65","author":"Blankman","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"2026090205180773800_cit8","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/nm803","article-title":"Modulation of Anxiety\nthrough Blockade of Anandamide Hydrolysis","volume":"9","author":"Kathuria","year":"2003","journal-title":"Nat.\nMed."},{"key":"2026090205180773800_cit9","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1021\/ml100190t","article-title":"Discovery\nof PF-04457845: A Highly Potent, Orally Bioavailable, and Selective\nUrea FAAH Inhibitor","volume":"2","author":"Johnson","year":"2011","journal-title":"ACS Med. Chem. Lett."},{"key":"2026090205180773800_cit10","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1124\/jpet.111.180257","article-title":"Mechanistic and\nPharmacological Characterization of PF-04457845: A Highly Potent and\nSelective Fatty Acid Amide Hydrolase Inhibitor That Reduces Inflammatory\nand Noninflammatory Pain","volume":"338","author":"Ahn","year":"2011","journal-title":"J. Pharmacol. Exp.\nTher."},{"key":"2026090205180773800_cit11","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1111\/j.1365-2125.2011.04137.x","article-title":"Assessment\nof the Pharmacology and\nTolerability of PF-04457845, an Irreversible Inhibitor of Fatty Acid\nAmide Hydrolase-1, in Healthy Subjects: Pharmacology and Tolerability\nof PF-04457845","volume":"73","author":"Li","year":"2012","journal-title":"Br. J. Clin. Pharmacol."},{"key":"2026090205180773800_cit12","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/j.pain.2012.04.020","article-title":"An Efficient\nRandomised, Placebo-Controlled Clinical Trial with the Irreversible\nFatty Acid Amide Hydrolase-1 Inhibitor PF-04457845, Which Modulates\nEndocannabinoids but Fails to Induce Effective Analgesia in Patients\nwith Pain due to Osteoarthritis of the Knee","volume":"153","author":"Huggins","year":"2012","journal-title":"Pain"},{"key":"2026090205180773800_cit13","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1021\/jm900324e","article-title":"Synthesis,\nIn Vitro and In Vivo Evaluation,\nand Radiolabeling of Aryl Anandamide Analogues as Candidate Radioligands\nfor In Vivo Imaging of Fatty Acid Amide Hydrolase in the Brain","volume":"52","author":"wyffels","year":"2009","journal-title":"J. Med. Chem."},{"key":"2026090205180773800_cit14","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.nucmedbio.2013.04.008","article-title":"Synthesis and Preclinical Evaluation\nof [11C-carbonyl]PF-04457845 for Neuroimaging\nof Fatty Acid Amide Hydrolase","volume":"40","author":"Hicks","year":"2013","journal-title":"Nucl. Med. Biol."},{"key":"2026090205180773800_cit15","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/j.nucmedbio.2012.03.011","article-title":"The Synthesis and In Vivo Evaluation\nof [18F]PF-9811: A Novel PET Ligand for Imaging Brain Fatty\nAcid Amide\nHydrolase (FAAH)","volume":"39","author":"Skaddan","year":"2012","journal-title":"Nucl. Med. Biol."},{"key":"2026090205180773800_cit16","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1021\/ml4000996","article-title":"Discovery of MK-3168:\nA PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase","volume":"4","author":"Liu","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"2026090205180773800_cit17","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.nucmedbio.2010.03.009","article-title":"PET Imaging of Fatty Acid Amide Hydrolase\nin the Brain: Synthesis and Biological Evaluation of an 11C-Labelled URB597 Analogue","volume":"37","author":"wyffels","year":"2010","journal-title":"Nucl. Med. Biol."},{"key":"2026090205180773800_cit18","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.nucmedbio.2010.08.001","article-title":"[11C]CURB:\nEvaluation of a Novel Radiotracer\nfor Imaging Fatty Acid Amide Hydrolase by Positron Emission Tomography","volume":"38","author":"Wilson","year":"2011","journal-title":"Nucl. Med. Biol."},{"key":"2026090205180773800_cit19","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1021\/jm301492y","article-title":"Radiosynthesis and\nEvaluation of [11C-carbonyl]-Labeled Carbamates\nas Fatty Acid Amide Hydrolase Radiotracers for Positron Emission Tomography","volume":"56","author":"Wilson","year":"2013","journal-title":"J. Med. Chem."},{"key":"2026090205180773800_cit20","doi-asserted-by":"crossref","first-page":"5621","DOI":"10.1039\/c3cc42236d","article-title":"11CO2 Fixation:\nA Renaissance in PET Radiochemistry","volume":"49","author":"Rotstein","year":"2013","journal-title":"Chem. Commun."},{"key":"2026090205180773800_cit21","first-page":"397","article-title":"Translational Studies\nwith [11C]MK-3168,\na PET Tracer for Fatty Acid Amide Hydrolase (FAAH)","volume":"53","author":"Joshi","year":"2012","journal-title":"Soc. Nucl. Med. Annu. Meet. Abstr."},{"key":"2026090205180773800_cit22","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/jcbfm.2012.180","article-title":"Mapping Human\nBrain Fatty Acid Amide Hydrolase Activity with PET","volume":"33","author":"Rusjan","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"2026090205180773800_cit23","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.chembiol.2005.08.011","article-title":"Mechanism of Carbamate Inactivation of FAAH: Implications\nfor the Design of Covalent Inhibitors and In Vivo Functional Probes\nfor Enzymes","volume":"12","author":"Alexander","year":"2005","journal-title":"Chem. Biol."},{"key":"2026090205180773800_cit24","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0009-3084(00)00190-0","article-title":"The Fatty\nAcid Amide\nHydrolase (FAAH)","volume":"108","author":"Ueda","year":"2000","journal-title":"Chem. Phys. Lipids"},{"key":"2026090205180773800_cit25","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0169-328X(02)00167-5","article-title":"Fatty Acid Amide Hydrolase\nLocalization in the Human Central Nervous System: An Immunohistochemical\nStudy","volume":"100","author":"Romero","year":"2002","journal-title":"Mol. Brain Res."},{"key":"2026090205180773800_cit26","doi-asserted-by":"crossref","first-page":"4351","DOI":"10.1016\/j.bmc.2013.04.077","article-title":"Development and Characterization\nof a Promising Fluorine-18\nLabelled Radiopharmaceutical for In Vivo Imaging of Fatty Acid Amide\nHydrolase","volume":"21","author":"Sadovski","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"2026090205180773800_cit27","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.neuropharm.2006.11.009","article-title":"Fatty Acid\nAmide Hydrolase Inhibitors Display Broad Selectivity and Inhibit Multiple\nCarboxylesterases as off-Targets","volume":"52","author":"Zhang","year":"2007","journal-title":"Neuropharmacology"},{"key":"2026090205180773800_cit28","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/j.bcp.2005.09.002","article-title":"Butyrylcholinesterase,\nParaoxonase,\nand Albumin Esterase, but Not Carboxylesterase, Are Present in Human\nPlasma","volume":"70","author":"Li","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"2026090205180773800_cit29","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/pola.21159","article-title":"Synthesis\nand Polymerization Reactions\nof Cyclic Imino Ethers. I. Ring-Opening Homopolyaddition of AB-Type\nHydroxyphenyl-Substituted 2-Oxazolines","volume":"44","author":"Luston\u030c","year":"2006","journal-title":"J. Polym.\nSci., Part A: Polym. Chem."},{"key":"2026090205180773800_cit30","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1006\/nimg.2001.0752","article-title":"Template\nImages for Nonhuman Primate Neuroimaging: 1. Baboon","volume":"14","author":"Black","year":"2001","journal-title":"NeuroImage"},{"key":"2026090205180773800_cit31","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1097\/00004647-199910000-00012","article-title":"Kinetic Modeling of N-[11C]Methylpiperidin-4-yl Propionate: Alternatives for Analysis of an\nIrreversible Positron Emission Tomography Tracer for Measurement of\nAcetylcholinesterase Activity in Human Brain","volume":"19","author":"Koeppe","year":"1999","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"2026090205180773800_cit32","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1124\/jpet.104.069401","article-title":"Reversible Inhibitors\nof Fatty Acid Amide Hydrolase That Promote Analgesia: Evidence for\nan Unprecedented Combination of Potency and Selectivity","volume":"311","author":"Lichtman","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2026090205180773800_cit33","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/j.1476-5381.2011.01388.x","article-title":"The Fatty Acid Amide Hydrolase Inhibitor URB 597: Interactions\nwith Anandamide in Rhesus Monkeys","volume":"164","author":"Stewart","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"2026090205180773800_cit34","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/7657_2012_53","article-title":"The Assay of Enzyme\nActivity by Positron Emission Tomography","volume-title":"Molecular Imaging in the Clinical Neurosciences","author":"Cumming","year":"2012"},{"key":"2026090205180773800_cit35","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1258\/la.2012.011173","article-title":"Anaesthesia for Positron Emission Tomography Scanning\nof Animal Brains","volume":"47","author":"Alstrup","year":"2013","journal-title":"Lab. Anim."}],"container-title":["Molecular Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/mp500316h","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article-pdf\/11\/11\/3832\/14372165\/mp500316h.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article-pdf\/11\/11\/3832\/14372165\/mp500316h.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:18:14Z","timestamp":1788340694000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article\/11\/11\/3832\/1379561\/PET-Imaging-of-Fatty-Acid-Amide-Hydrolase-with-18F"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,8]]},"references-count":35,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,7,8]]},"published-print":{"date-parts":[[2014,11,3]]}},"URL":"https:\/\/doi.org\/10.1021\/mp500316h","relation":{},"ISSN":["1543-8384","1543-8392"],"issn-type":[{"value":"1543-8384","type":"print"},{"value":"1543-8392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,8]]}}}