{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:11:14Z","timestamp":1791519074285,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Radboud Institute for Molecular Life Sciences (RIMLS)","award":["KUN2015-8106"],"award-info":[{"award-number":["KUN2015-8106"]}]},{"name":"Radboud Oncologie Fonds (ROF)and Stichting Bergh in het Zadel, partner of Dutch Cancer Society","award":["KUN2015-8106"],"award-info":[{"award-number":["KUN2015-8106"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Fibroblast activation protein (FAP), expressed on cancer-associated fibroblasts, is a target for diagnosis and therapy in multiple tumour types. Strategies to systemically deplete FAP-expressing cells show efficacy; however, these induce toxicities, as FAP-expressing cells are found in normal tissues. FAP-targeted photodynamic therapy offers a solution, as it acts only locally and upon activation. Here, a FAP-binding minibody was conjugated to the chelator diethylenetriaminepentaacetic acid (DTPA) and the photosensitizer IRDye700DX (DTPA-700DX-MB). DTPA-700DX-MB showed efficient binding to FAP-overexpressing 3T3 murine fibroblasts (3T3-FAP) and induced the protein\u2019s dose-dependent cytotoxicity upon light exposure. Biodistribution of DTPA-700DX-MB in mice carrying either subcutaneous or orthotopic tumours of murine pancreatic ductal adenocarcinoma cells (PDAC299) showed maximal tumour uptake of 111In-labelled DTPA-700DX-MB at 24 h post injection. Co-injection with an excess DTPA-700DX-MB reduced uptake, and autoradiography correlated with FAP expression in the stromal tumour region. Finally, in vivo therapeutic efficacy was determined in two simultaneous subcutaneous PDAC299 tumours; only one was treated with 690 nm light. Upregulation of an apoptosis marker was only observed in the treated tumours. In conclusion, DTPA-700DX-MB binds to FAP-expressing cells and targets PDAC299 tumours in mice with good signal-to-background ratios. Furthermore, the induced apoptosis indicates the feasibility of targeted depletion of FAP-expressing cells with photodynamic therapy.<\/jats:p>","DOI":"10.3390\/cells12101420","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T06:00:29Z","timestamp":1684389629000},"page":"1420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Fibroblast Activation Protein-Targeting Minibody-IRDye700DX for Ablation of the Cancer-Associated Fibroblast with Photodynamic Therapy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8350-2131","authenticated-orcid":false,"given":"Esther M. M.","family":"Smeets","sequence":"first","affiliation":[{"name":"Department of Medical Imaging, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9292-0693","authenticated-orcid":false,"given":"Daphne N.","family":"Dorst","sequence":"additional","affiliation":[{"name":"Department of Experimental Rheumatology, Radboud Institute for Molecular Life Sciences, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerben M.","family":"Franssen","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merijn S.","family":"van Essen","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathelijne","family":"Frielink","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn W. J.","family":"Stommel","sequence":"additional","affiliation":[{"name":"Department of Surgery, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Trajkovic-Arsic","sequence":"additional","affiliation":[{"name":"Bridge Institute of Experimental Tumour Therapy, West German Cancer Centre, University Hospital Essen, University of Duisburg-Essen, 47057 Essen, Germany"},{"name":"Division of Solid Tumour Translational Oncology, German Cancer Consortium (DKTK Partner Site Essen) and German Cancer Research Centre, DKFZ, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phyllis F.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Bridge Institute of Experimental Tumour Therapy, West German Cancer Centre, University Hospital Essen, University of Duisburg-Essen, 47057 Essen, Germany"},{"name":"Division of Solid Tumour Translational Oncology, German Cancer Consortium (DKTK Partner Site Essen) and German Cancer Research Centre, DKFZ, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8772-4778","authenticated-orcid":false,"given":"Jens T.","family":"Siveke","sequence":"additional","affiliation":[{"name":"Bridge Institute of Experimental Tumour Therapy, West German Cancer Centre, University Hospital Essen, University of Duisburg-Essen, 47057 Essen, Germany"},{"name":"Division of Solid Tumour Translational Oncology, German Cancer Consortium (DKTK Partner Site Essen) and German Cancer Research Centre, DKFZ, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Wilson","sequence":"additional","affiliation":[{"name":"ImaginAb, Inglewood, CA 90301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Mascioni","sequence":"additional","affiliation":[{"name":"ImaginAb, Inglewood, CA 90301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3809-0182","authenticated-orcid":false,"given":"Erik H. J. G.","family":"Aarntzen","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8584-2546","authenticated-orcid":false,"given":"Sanne A. M.","family":"van Lith","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/B978-0-12-394308-8.00003-0","article-title":"Fibroblast activation protein-alpha: A key modulator of the microenvironment in multiple pathologies","volume":"297","author":"Kelly","year":"2012","journal-title":"Int. Rev. Cell Mol. 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