{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:54:41Z","timestamp":1791438881528,"version":"4.3.3"},"reference-count":23,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"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":[[2026,8,14]]},"abstract":"<jats:p>\n                    The pronounced lipophilicity of\n                    <jats:italic>tert<\/jats:italic>\n                    \u2010butyl\u2010substituted silicon\u2010fluoride\u2010acceptor (SiFA) scaffolds represents a major limitation in radiotracer development, often resulting in elevated nonspecific uptake and reduced tumor\u2010to\u2010background ratios. To address this challenge, we designed and synthesized a series of prostate\u2010specific membrane antigen (PSMA)\u2010targeted radioligands incorporating furanose\u2010 and pyranose\u2010based sugar amino acid (SAA) linkers to evaluate physicochemical properties while maintaining efficient\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010radiolabeling capability. Six compounds (\n                    <jats:bold>19<\/jats:bold>\n                    <jats:bold>\u201324<\/jats:bold>\n                    ) were prepared via a convergent three\u2010step synthesis in 35%\u201375% overall yield. Furanose\u2010SAA derivatives (\n                    <jats:bold>19\u201322<\/jats:bold>\n                    ) retained moderate PSMA binding affinity (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20095\u201319\u2009\u00b5M), while pyranose\u2010SAA analogues\n                    <jats:bold>23<\/jats:bold>\n                    and\n                    <jats:bold>24<\/jats:bold>\n                    were inactive (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009&gt;\u2009100\u2009\u00b5M). All compounds exhibited similar lipophilicity (log\n                    <jats:italic>P<\/jats:italic>\n                    = 3.10\u20133.42), indicating that the differences in biological activity are not primarily attributable to lipophilicity. Compounds\n                    <jats:bold>19<\/jats:bold>\n                    and\n                    <jats:bold>21<\/jats:bold>\n                    were radiolabeled via isotopic exchange in 25%\u201340% radiochemical yield with molar activity of 86\u2009\u00b1 3\u2009GBq\/\u00b5mol. PET imaging in LNCaP xenograft mice demonstrated that\n                    <jats:bold>\n                      [\n                      <jats:sup>18<\/jats:sup>\n                      F]21\n                    <\/jats:bold>\n                    , bearing three furanose\u2010SAA units, achieved SUV\n                    <jats:sub>60min<\/jats:sub>\n                    \u2009=\u20090.64\u2009\u00b1\u20090.06 with \u2009~30% blocking by DCFPyL, confirming partial PSMA\u2010mediated uptake. This proof\u2010of\u2010concept study establishes SAA linkers as a viable strategy for pharmacokinetic optimization of SiFA\u2010based radiotracers, warranting further structural refinement to enhance target affinity.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70436","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T03:18:58Z","timestamp":1786591138000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sugar Amino Acid Linkers for the Design\u00a0of [\n                    <sup>18<\/sup>\n                    F]SiFA\u2010PSMA Radioligands"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6786-2604","authenticated-orcid":false,"given":"Narendar R.","family":"Gade","sequence":"first","affiliation":[{"name":"Department of Oncology Cross Cancer Institute University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Wuest","sequence":"additional","affiliation":[{"name":"Department of Oncology Cross Cancer Institute University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-5712","authenticated-orcid":false,"given":"Justin J.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Oncology Cross Cancer Institute University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Department of Oncology Cross Cancer Institute University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7098-3036","authenticated-orcid":false,"given":"Ralf","family":"Schirrmacher","sequence":"additional","affiliation":[{"name":"Department of Oncology Cross Cancer Institute University of Alberta  Edmonton Alberta Canada"},{"name":"Department of Chemistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6705-6450","authenticated-orcid":false,"given":"Frank","family":"Wuest","sequence":"additional","affiliation":[{"name":"Department of Oncology Cross Cancer Institute University of Alberta  Edmonton Alberta Canada"},{"name":"Department of Chemistry University of Alberta  Edmonton Alberta Canada"},{"name":"Cancer Research Institute of Northern Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-004-1607-9"},{"issue":"1","key":"e_1_2_9_3_1","first-page":"55","article-title":"Positron Emission Tomography (PET) Imaging With (18)F\u2010Based Radiotracers","volume":"2","author":"Alauddin M. 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