{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:13:52Z","timestamp":1760235232932,"version":"build-2065373602"},"reference-count":15,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["323196"],"award-info":[{"award-number":["323196"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2180"],"award-info":[{"award-number":["EXC 2180"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The acidic hydrolase \u03b1-fucosidase (AF) is a biomarker for maladies such as cancer and inflammation. The most advanced probes for \u03b1-fucosidase are unfortunately constrained to ex vivo or in vitro applications. The in vivo detection and quantification of AF using positron emission tomography would allow for better discovery and diagnosis of disease as well as provide better understanding of disease progression. We synthesized, characterized, and evaluated a radiolabeled small molecule inhibitor of AF based on a known molecule. The radiosynthesis involved the 11C methylation of a phenoxide, which was generated in situ by ultrasonification of the precursor with sodium hydride. The tracer was produced with a decay corrected yield of 41.7 \u00b1 16.5% and had a molar activity of 65.4 \u00b1 30.3 GBq\/\u03bcmol. The tracer was shown to be stable in mouse serum at 60 min. To test the new tracer, HCT116 colorectal carcinoma cells were engineered to overexpress human AF. In vitro evaluation revealed 3.5-fold higher uptake in HCT116AF cells compared to HCT116 controls (26.4 \u00b1 7.8 vs. 7.5 \u00b1 1.0 kBq\/106 cells). Static PET scans 50 min post injection revealed 2.5-fold higher tracer uptake in the HCT116AF tumors (3.0 \u00b1 0.8%ID\/cc (n = 6)) compared with the controls (1.2 \u00b1 0.8 (n = 5)). Dynamic scans showed higher uptake in the HCT116AF tumors at all time-points (n = 2). Ex vivo analysis of the tumors, utilizing fluorescent DDK2 antibodies, confirmed the expression of human AF in the HCT116AF xenografts. We have developed a novel PET tracer to image AF in vivo and will now apply this to relevant disease models.<\/jats:p>","DOI":"10.3390\/ph14080745","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T21:21:21Z","timestamp":1627593681000},"page":"745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Biological Evaluation of a Radiolabeled PET (Positron Emission Tomography) Probe for Visualization of In Vivo \u03b1-Fucosidase Expression"],"prefix":"10.3390","volume":"14","author":[{"given":"Jonathan","family":"Cotton","sequence":"first","affiliation":[{"name":"Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC 2180) \u201cImage Guided and Functionally Instructed Tumor Therapies\u201d, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris Marc","family":"Goehring","sequence":"additional","affiliation":[{"name":"Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kuehn","sequence":"additional","affiliation":[{"name":"Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2412-5361","authenticated-orcid":false,"given":"Andreas","family":"Maurer","sequence":"additional","affiliation":[{"name":"Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC 2180) \u201cImage Guided and Functionally Instructed Tumor Therapies\u201d, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd J.","family":"Pichler","sequence":"additional","affiliation":[{"name":"Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC 2180) \u201cImage Guided and Functionally Instructed Tumor Therapies\u201d, Eberhard Karls University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s11010-014-1961-2","article-title":"Modulation of Expression in BEAS-2B Airway Epithelial Cells of \u03b1-l-Fucosidase A1 and A2 by Th1 and Th2 Cytokines, and Overexpression of \u03b1-l-Fucosidase 2","volume":"390","author":"Sobkowicz","year":"2014","journal-title":"Mol. 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