{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T22:01:51Z","timestamp":1780178511478,"version":"3.54.0"},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,5,27]]},"abstract":"<jats:p>\n                    Most prostate specific membrane antigen (PSMA)\u2010targeted drugs contain a urea\u2010based targeting vector, although high PSMA\u2010binding affinities have also been realized with other zinc\u2010binding motifs. This study describes the synthesis and evaluation of a hybrid compound containing a phosphinate motif (GPI) and a linker derived from an established urea\u2010based PSMA ligand (PSMA\u2010617). Fluorescent conjugates differing in their zinc\u2010binding motif only were synthesized and evaluated in\u2009vitro and in\u2009vivo. The phosphinate hybrid Cy5\u2010GPI617 (\n                    <jats:bold>9<\/jats:bold>\n                    ) is more polar and has reduced binding affinity to human serum albumin (HSA) compared to its urea analog Cy5\u2010617 (\n                    <jats:bold>10<\/jats:bold>\n                    ). At the same time, Cy5\u2010GPI617 (\n                    <jats:bold>9<\/jats:bold>\n                    ) has an almost identical PSMA binding affinity (low nM) and leads to high, PSMA\u2010specific cellular uptake. In\u2009vivo, the phosphinate hybrid\n                    <jats:bold>9<\/jats:bold>\n                    showed reduced retention in nontumor tissues along with only moderately decreased tumor uptake compared to the urea analog\n                    <jats:bold>10<\/jats:bold>\n                    . These findings demonstrate that the previously performance\u2010limiting phosphate competition of GPI can be overcome by molecular engineering and highlight the potential of phosphinate\u2010based scaffolds for PSMA targeting.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70320","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T04:31:08Z","timestamp":1779856268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phosphinate or Urea? Synthesis and Biological Evaluation of Prostate Specific Membrane Antigen\u2010Targeted Fluorophores With Different Zinc\u2010Binding Motif"],"prefix":"10.1002","volume":"21","author":[{"given":"Lennart F. V.","family":"Spickschen","sequence":"first","affiliation":[{"name":"Department of Chemistry Institute of Pharmacy University of Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Kerpa","sequence":"additional","affiliation":[{"name":"Department of Chemistry Institute of Pharmacy University of Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetiana","family":"Titko","sequence":"additional","affiliation":[{"name":"Department of Chemistry Institute of Pharmacy University of Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Th\u00fcnauer","sequence":"additional","affiliation":[{"name":"Technology Platform Light Microscopy (TPLM) University of Hamburg and Advanced Light and Fluorescence Microscopy (ALFM) Facility Centre of Structural Systems Biology  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Van Wazer","sequence":"additional","affiliation":[{"name":"Department of Radiology School of MedicineWashington University  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Fears","sequence":"additional","affiliation":[{"name":"Department of Radiology School of MedicineWashington University  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Cao","sequence":"additional","affiliation":[{"name":"EMIT Imaging Inc.  Natick Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Silva","sequence":"additional","affiliation":[{"name":"EMIT Imaging Inc.  Natick Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L. J.","family":"Thorek","sequence":"additional","affiliation":[{"name":"Department of Radiology School of MedicineWashington University  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Oetjen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology and Toxicology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2793-5722","authenticated-orcid":false,"given":"Wolfgang","family":"Maison","sequence":"additional","affiliation":[{"name":"Department of Chemistry Institute of Pharmacy University of Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12254-025-01043-6"},{"key":"e_1_2_9_3_1","first-page":"1545","article-title":"PSMA Ligands for PET Imaging of Prostate Cancer","volume":"58","author":"Schwarzenboeck S. 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