{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:10:27Z","timestamp":1785247827978,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21CA246413"],"award-info":[{"award-number":["R21CA246413"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA271532"],"award-info":[{"award-number":["R01CA271532"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018138","name":"Kuni Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018138","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Positive surgical margins following radical prostatectomy increase the risk of biochemical recurrence and subsequent disease progression. Fluorescence\u2010guided surgery (FGS) using targeted contrast agents has shown clinical benefits for several cancer types. However, current prostate cancer targeted imaging probes exhibit long pharmacokinetic (PK) profiles, necessitating extended waiting periods or repeated hospital visits, limiting their integration into standard clinical workflow. To overcome this critical clinical compatibility challenge, we developed an innovative tri\u2010compartment, chemistry\u2010driven probe design strategy. Specifically, we developed a congeneric library of near infrared (NIR) water soluble fluorescent probes incorporating: 1) a glutamic acid\u2010urea\u2010lysine (EuK) ligand targeting prostate specific membrane antigen (PSMA); 2) a NIR heptamethine cyanine fluorophore optimized for enhanced PSMA binding via secondary binding site interactions; and 3) distinct PK modulators residing outside the PSMA binding pocket to promote rapid off\u2010target tissue clearance. While molecular docking scores, photophysical properties and live\u2010cell staining results showed similar overall performance, probes bearing PK modulators produced stronger tumor\u2010specific fluorescence and accumulation in vivo than the control probe lacking a PK modulator. This effort enabled identification of a lead probe with robust tumor targeting and accelerated off\u2010target clearance, providing optimal tumor\u2010specific signal and contrast in a timeframe, fully compatible with robotic\u2010assisted radical prostatectomy (RARP) timelines.<\/jats:p>","DOI":"10.1002\/anie.202520355","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T02:46:22Z","timestamp":1765593982000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Engineering NIR Probes to Enhance Affinity and Clinical Workflow Compatibility for Prostate Cancer Imaging"],"prefix":"10.1002","volume":"65","author":[{"given":"Gauri S.","family":"Malankar","sequence":"first","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani A.","family":"Szafran","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gourav","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Pace","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Devereux","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Oregon Health &amp; Science University  Portland Oregon 97201 USA"},{"name":"Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Tao","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Oregon Health &amp; Science University  Portland Oregon 97201 USA"},{"name":"Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Gomes","sequence":"additional","affiliation":[{"name":"Cancer Early Detection Advanced Research Center Oregon Health &amp; Science University  Portland Oregon 97201 USA"},{"name":"Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Greer","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody C.","family":"Rounds","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas M.","family":"Masillati","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seseel","family":"Gergis","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayden","family":"Ledvina","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle J.","family":"Milnes","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa H.","family":"Wong","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon 97201 USA"},{"name":"Department of Cell, Developmental and Cancer Biology Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Niedre","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Northeastern University  Boston Massachusetts 02115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Summer L.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"},{"name":"Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0664-2704","authenticated-orcid":false,"given":"Lei G.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department Biomedical Engineering Oregon Health &amp; Science University  Portland Oregon 97201 USA"},{"name":"Knight Cancer Institute, Oregon Health &amp; Science University  Portland Oregon 97201 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2023.12.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606221"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201051598\u20103"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/end.2023.0188"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2012.09.033"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.16732"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14010013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajur.2022.02.014"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.pcan.4500612"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970\u20101591.134240"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41391\u2010024\u201000868\u20102"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2014.09.006"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097\u20100142(19981201)83:11"},{"key":"e_1_2_8_15_1","first-page":"6357","volume":"9","author":"Ross J. S.","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.9b00758"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201025746\u20106"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b04412"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.36739"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc2002715"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/ml400533y"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.10.013"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1373606"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115966"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15184537"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17091401"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14080713"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11307\u2010016\u20100957\u20106"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.6b00093"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.21.2601"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2013.123"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2023.102361"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2021.825183"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(19)30317\u20101"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2223\u20104292.2012.09.04"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2003.08.007"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.3065"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.07.010"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549\u2010018\u20104845\u20104"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2023.07.004"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(23)00102\u2010X"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2468"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.2c00083"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja104591m"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2018.03.015"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215549904700910"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b11925"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202406694"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1117\/1.JBO.27.9.097002"},{"key":"e_1_2_8_50_1","doi-asserted-by":"crossref","unstructured":"A.Williams M. i.Niedre Biophotonics Congress: Optics in the Life Sciences 2023 (OMA NTM BODA OMP BRAIN). OM4E.4 (Optica Publishing Group) https:\/\/doi.org\/10.1364\/OMP.2023.OM4E.4.","DOI":"10.1364\/OMP.2023.OM4E.4"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1914913117"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/33.6.765"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.21037\/tau.2019.09.15"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41391\u2010018\u20100104\u20103"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay0712"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123190"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202520355","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202520355","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202520355","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T13:37:16Z","timestamp":1785245836000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202520355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":56,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2026,7,27]]}},"alternative-id":["10.1002\/anie.202520355"],"URL":"https:\/\/doi.org\/10.1002\/anie.202520355","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.09.16.676549","asserted-by":"object"}]},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]},"assertion":[{"value":"2025-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e20355"}}