{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T11:11:16Z","timestamp":1776510676717,"version":"3.51.2"},"reference-count":45,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Prostate\u2010specific membrane antigen (PSMA) is increasingly recognized as an excellent target for prostate cancer imaging and therapy. Finding compounds with a high target\u2010to\u2010nontarget ratio are an important challenge in the development of positron emission tomography (PET) imaging agents. In this study, we attempted to find a suitable compound from a simply\u2010synthesized compound library.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p><jats:sup>18<\/jats:sup>F\u2010labeling was achieved in a two\u2010step synthesis consisting of [<jats:sup>18<\/jats:sup>F]fluorination of azido sulfonates followed by copper(I)\u2010catalyzed click ligation. In vitro binding experiment and in vivo studies were carried out using isogenic PSMA+ PC3\u2010PIP and PSMA\u2212 PC3\u2010flu cells and 22RV1 cells. [<jats:sup>125<\/jats:sup>I]MIP\u20101095 was used to measure the binding affinities of compounds through a competitive binding assay, and [<jats:sup>18<\/jats:sup>F]DCFPyL was used for a comparative assessment of compounds. Radiation dosimetry data were obtained using OLINDA\/EXM software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nine novel PSMA ligands were synthesized by the combination of three azido compounds and three terminal acetylene\u2010containing Glu\u2010urea\u2010Lys compounds. Among them, compound <jats:bold>6f<\/jats:bold> having a pyridine moiety showed a high binding affinity of 6.51\u2009\u00b1\u20090.19\u2009nM (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>). <jats:sup>18<\/jats:sup>F\u2010labeled compounds were obtained at moderate yields within 70 to 75\u2009minutes (including high\u2010performance liquid chromatography purification). Compound [<jats:sup>18<\/jats:sup>F]<jats:bold>6c<\/jats:bold> had the lowest log <jats:italic>P<\/jats:italic> of \u22122.693. MicroPET\/computed tomography (CT) images were acquired from 22RV1 cell xenograft mice after injecting [<jats:sup>18<\/jats:sup>F]<jats:bold>6c<\/jats:bold>, [<jats:sup>18<\/jats:sup>F]<jats:bold>6f<\/jats:bold>, and [<jats:sup>18<\/jats:sup>F]<jats:bold>6i<\/jats:bold>. Additional microPET\/CT experiments of [<jats:sup>18<\/jats:sup>F]<jats:bold>6c<\/jats:bold> and [<jats:sup>18<\/jats:sup>F]<jats:bold>6f<\/jats:bold> were performed using PSMA+ PC3\u2010PIP and PSMA\u2212 PC3\u2010flu cell\u2010bearing mice. [<jats:sup>18<\/jats:sup>F]<jats:bold>6c<\/jats:bold> was selected for further studies because it was found to have high uptake in tumors and rapid renal clearance, resulting in great tumor\u2010to\u2010nontumor ratios and distinct tumor images with very low background activity. Human dosimetry estimation of [<jats:sup>18<\/jats:sup>F]<jats:bold>6c<\/jats:bold> using OLINDA\/EXM software was calculated, resulting in an effective dose of 4.35\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>\u2009mSv\/MBq.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>[<jats:sup>18<\/jats:sup>F]<jats:bold>6c<\/jats:bold> showed significant tumor uptake, a high tumor\u2010to\u2010nontumor ratio, and good radiation dosimetry results, suggesting further development as a potential diagnostic PET agent for prostate cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24062","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:44:35Z","timestamp":1600821875000},"page":"1383-1393","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<sup>18<\/sup>F\u2010labeled 1,2,3\u2010triazole\u2010linked Glu\u2010urea\u2010Lys\u2010based PSMA ligands have good pharmacokinetic properties for positron emission tomography imaging of prostate cancer"],"prefix":"10.1002","volume":"80","author":[{"given":"Byoung Se","family":"Lee","sequence":"first","affiliation":[{"name":"Research Institute of Labeling FutureChem Co., Ltd. Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Young","family":"Chu","sequence":"additional","affiliation":[{"name":"Research Institute of Labeling FutureChem Co., Ltd. Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woon Jung","family":"Jung","sequence":"additional","affiliation":[{"name":"Research Institute of Labeling FutureChem Co., Ltd. Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeon Jin","family":"Jeong","sequence":"additional","affiliation":[{"name":"Research Institute of Labeling FutureChem Co., Ltd. Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyongkyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Institute of Labeling FutureChem Co., Ltd. Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Institute of Labeling FutureChem Co., Ltd. Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Institute of Labeling FutureChem Co., Ltd. Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9862-3286","authenticated-orcid":false,"given":"Dae Yoon","family":"Chi","sequence":"additional","affiliation":[{"name":"Research Institute of Labeling FutureChem Co., Ltd. Seoul Republic of Korea"},{"name":"Department of Chemistry Sogang University Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heesu","family":"Ahn","sequence":"additional","affiliation":[{"name":"Division of Applied RI Korea Institute of Radiological and Medical Sciences Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Applied RI Korea Institute of Radiological and Medical Sciences Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8863-6702","authenticated-orcid":false,"given":"Kyo Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Applied RI Korea Institute of Radiological and Medical Sciences Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang 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