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Although serum prostate\u2010specific antigen (PSA) testing is prevalent for PCa screening, its inherent limitation in specificity and sensitivity frequently leads to high false\u2010positive and false\u2010negative diagnoses. To address this challenge, we present a PSA+ strategy that integrates a clinically defined PSA threshold (10\u00a0ng\/mL) with a pair of complementary near\u2010infrared (NIR) fluorescent probes: a zinc\u2010complex\u2010based probe (Cy\u2010O\u2010NS\u2010a\u2010Zn) targeting the zinc transporter solute carrier family 39 member 1 (SLC39A1), and a glutamate\u2010urea\u2010lysine (Glu\u2010Urea\u2010Lys) ligand\u2010based probe (Cy\u2010S\u2010Glu) targeting prostate\u2010specific membrane antigen (PSMA). This combinatorial approach accurately discriminates PCa from normal prostate cells, delineates tumor margins in patient\u2010derived xenograft (PDX) mouse models with robust tumor\u2010to\u2010background ratios (TBR), and enables fluorescence\u2010guided surgery. Importantly, a double\u2010blind histopathological validation using 70 cases of human prostate tissue specimens revealed that the PSA+ strategy substantially outperformed PSA testing alone, improving diagnostic specificity from 70% to 97.6% and sensitivity from 75% to 96.8%. Collectively, this work provides a rapid, accurate, and comprehensive diagnostic paradigm that complements standard PSA testing, thereby refining clinical diagnosis and decision\u2010making in PCa.<\/jats:p>","DOI":"10.1002\/anie.9280379","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:19:31Z","timestamp":1787728771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Boosting Diagnostic Accuracy of Prostate Cancer: Combining Clinical PSA Level and a Pair of NIR Fluorescent Probes for SLC39A1 and PSMA"],"prefix":"10.1002","volume":"65","author":[{"given":"Xiuzhu","family":"Huo","sequence":"first","affiliation":[{"name":"Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education Xi'an Key Laboratory of Photo\u2010functional Molecular Materials and Theranostic Institute of Chemical Biology of Northwest University College of Chemistry &amp; 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Key Laboratory of Shaanxi Province Laboratory of Tissue Engineering the College of Life Sciences Faculty of Life Science &amp; Medicine Northwest University Xi'an Shaanxi Province China"},{"name":"Shaanxi Key Laboratory For Carbon Neutral Technology Carbon Neutrality College (YuLin) Northwest University  Yulin Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education Xi'an Key Laboratory of Photo\u2010functional Molecular Materials and Theranostic Institute of Chemical Biology of Northwest University College of Chemistry &amp; Materials Science Northwest 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