{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:09:46Z","timestamp":1785409786842,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["423813989\/GRK2606"],"award-info":[{"award-number":["423813989\/GRK2606"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"award":["423813989\/GRK2606"],"award-info":[{"award-number":["423813989\/GRK2606"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Objectives: Fluorescence-guided surgery (FGS) targeting prostate-specific membrane antigen (PSMA) holds promise for improving surgical precision in prostate cancer. Since conjugation of fluorescent dyes to targeting vectors can substantially alter pharmacokinetic properties, we systematically evaluated a library of fluorescent dyes conjugated to a PSMA-617-derived scaffold incorporating sarcosine-based spacers to identify candidates with favorable biodistribution and optical profiles for clinical translation. Methods: Nineteen fluorescent dyes spanning NIR, large Stokes shift, and STED-compatible categories were conjugated to a dual-labeled PSMA-617-derived precursor (Glu-urea-Lys-2Nal-TXA-Sar10-Lys(DOTA)-Sar5-\u03b2Ala; hereafter DP). Compounds were radiolabeled with 68Ga or 177Lu and characterized for serum stability, lipophilicity, binding affinity, and internalization in LNCaPPSMA+ cells. In vivo pharmacokinetics were assessed in LNCaP xenograft-bearing BALB\/c nu\/nu mice by \u00b5PET\/MRI (1 and 2 h p.i., 500 pmol 68Ga), organ distribution (0.5, 1, and 2 h p.i., 60 pmol 177Lu), and clinical-grade endoscopic fluorescence imaging. Results: All conjugates retained hydrophilic character (logD: \u22123.72 to \u22121.79), low nanomolar binding affinity (Ki: 18\u201387 nM), and high serum stability (94\u2013100% intact at 24 h). Despite comparable in vitro properties, dye conjugation markedly influenced in vivo pharmacokinetics: tumor uptake at 2 h p.i. ranged from 1 to 23%ID\/g and kidney accumulation from 3 to 82%ID\/g. Visible-range dyes exhibited faster renal washout within the imaging window and higher tumor-to-background contrast than NIR fluorophores. Fluorescence signal intensity did not correlate with radiotracer-derived uptake, underscoring the importance of dye-specific photophysical properties. Conclusions: DP-12 (SulfoCy5), DP-15 (Alexa Fluor 647), and DP-18 (Tide Fluor 5WS) were identified as lead candidates combining favorable pharmacokinetics with strong fluorescence contrast, warranting further evaluation toward fluorescence-guided prostate cancer surgery.<\/jats:p>","DOI":"10.3390\/ph19081187","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:45:14Z","timestamp":1785325514000},"page":"1187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sarcosine-Based Pharmacokinetic Optimization and Fluorescent Dye Library Evaluation of Dual-Labeled PSMA Inhibitors for Fluorescence-Guided Surgery"],"prefix":"10.3390","volume":"19","author":[{"given":"Paul","family":"Minges","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Division of Radiopharmaceutical Development, German Consortium for Translational Cancer Research (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Department of Biology, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6560-2174","authenticated-orcid":false,"given":"Jessica","family":"Matthias","sequence":"additional","affiliation":[{"name":"Abberior GmbH, 37077 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa-Charlotte","family":"Domogalla","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Division of Radiopharmaceutical Development, German Consortium for Translational Cancer Research (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Thomas","sequence":"additional","affiliation":[{"name":"XION GmbH, 13127 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Steinacker","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Division of Radiopharmaceutical Development, German Consortium for Translational Cancer Research (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2509-6630","authenticated-orcid":false,"given":"Nawal Ayada","family":"Amgar","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Division of Radiopharmaceutical Development, German Consortium for Translational Cancer Research (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"XION GmbH, 13127 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Dietzel-Schaarschmidt","sequence":"additional","affiliation":[{"name":"Henke-Sass, Wolf GmbH, 78532 Tuttlingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp T.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Division of Radiopharmaceutical Development, German Consortium for Translational Cancer Research (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Eder","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Division of Radiopharmaceutical Development, German Consortium for Translational Cancer Research (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5858-469X","authenticated-orcid":false,"given":"Ann-Christin","family":"Eder","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Division of Radiopharmaceutical Development, German Consortium for Translational Cancer Research (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.eururo.2024.11.013","article-title":"Recent Patterns and Trends in Global Prostate Cancer Incidence and Mortality: An Update","volume":"87","author":"Schafer","year":"2025","journal-title":"Eur. 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