{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:13:28Z","timestamp":1791288808772,"version":"4.3.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T00:00:00Z","timestamp":1458604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Labelled Comp Radiopharmac"],"published-print":{"date-parts":[[2016,5,15]]},"abstract":"<jats:p>Phosphodiesterase (PDE) 4 is the most prevalent PDE in the central nervous system (CNS) and catalyzes hydrolysis of intracellular cAMP, a secondary messenger. By therapeutic inhibition of PDE4, intracellular cAMP levels can be stabilized, and the symptoms of psychiatric and neurodegenerative disorders including depression, memory loss and Parkinson's disease can be ameliorated. Radiotracers targeting PDE4 can be used to study PDE4 density and function, and evaluate new PDE4 therapeutics, <jats:italic>in vivo<\/jats:italic> in a non\u2010invasive way, as has been shown using the carbon\u201011 labeled PDE4 inhibitor <jats:italic>R<\/jats:italic>\u2010(\u2212)\u2010rolipram. Herein we describe a small series of rolipram analogs that contain fluoro\u2010 or iodo\u2010substituents that could be used as fluorine\u201018 PET or iodine\u2010123 SPECT PDE4 radiotracers. This series was evaluated with an <jats:italic>in vitro<\/jats:italic> binding assay and a 4\u2010(fluoromethyl) derivative of rolipram, MNI\u2010617, was identified, with a five\u2010fold increase in affinity for PDE4 (<jats:italic>K<\/jats:italic><jats:sub>d<\/jats:sub>\u2009=\u20090.26\u2009nM) over <jats:italic>R<\/jats:italic>\u2010(\u2212)\u2010rolipram (<jats:italic>K<\/jats:italic><jats:sub>d<\/jats:sub>\u2009=\u20091.6\u2009nM). A deutero\u2010analogue <jats:italic>d<jats:sub>2<\/jats:sub><\/jats:italic>\u2010[<jats:sup>18<\/jats:sup>F]MNI\u2010617 was radiolabeled and produced in 23% yield with high (&gt;5\u2009Ci\/\u00b5mol) specific activity and evaluated in non\u2010human primate, where it rapidly entered the brain, with SUVs between 4 and 5, and with a distribution pattern consistent with that of PDE4.<\/jats:p>","DOI":"10.1002\/jlcr.3389","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T21:06:36Z","timestamp":1458680796000},"page":"205-213","source":"Crossref","is-referenced-by-count":11,"title":["Identification and <i>in vivo<\/i> evaluation of a fluorine\u201018 rolipram analogue, [<sup>18<\/sup>F]MNI\u2010617, as a radioligand for PDE4 imaging in mammalian brain"],"prefix":"10.1002","volume":"59","author":[{"given":"David","family":"Thomae","sequence":"first","affiliation":[{"name":"Molecular NeuroImaging LLC  New Haven CT 06510 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Morley","sequence":"additional","affiliation":[{"name":"Molecular NeuroImaging LLC  New Haven CT 06510 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiaoju S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Molecular NeuroImaging LLC  New Haven CT 06510 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Barret","sequence":"additional","affiliation":[{"name":"Molecular NeuroImaging LLC  New Haven CT 06510 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Molecular NeuroImaging LLC  New Haven CT 06510 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Papin","sequence":"additional","affiliation":[{"name":"Molecular NeuroImaging LLC  New Haven CT 06510 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Molecular NeuroImaging LLC  New Haven CT 06510 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles D.","family":"Tamagnan","sequence":"additional","affiliation":[{"name":"Molecular NeuroImaging LLC  New Haven CT 06510 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Alagille","sequence":"additional","affiliation":[{"name":"Molecular NeuroImaging LLC  New Haven CT 06510 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,22]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.145"},{"key":"e_1_2_5_3_1","first-page":"311","volume":"12","author":"Whalin M. 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