{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:27:26Z","timestamp":1768282046242,"version":"3.49.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Royal Library, Copenhagen University Library"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Imaging Biol"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>[<jats:sup>64<\/jats:sup>Cu]Cu-DOTA-AE105 urokinase-type plasminogen activator receptor (uPAR)-PET\/CT is a novel and promising imaging modality for cancer visualization, although it has not been tested in head and neck cancer patients nor in preclinical models that closely resemble these heterogenous tumors, i.e., patient-derived xenograft (PDX) models. The aim of the present study was to establish and validate oral squamous cell carcinoma (OSCC) PDX models and to evaluate [<jats:sup>64<\/jats:sup>Cu]Cu-uPAR-PET\/CT for tumor imaging in these models.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Procedures<\/jats:title>\n                <jats:p>PDX flank tumor models were established by engrafting tumor tissue from three patients with locally advanced OSCC into immunodeficient mice. [<jats:sup>64<\/jats:sup>Cu]Cu-DOTA-AE105 was injected in passage 2 (P2) mice, and [<jats:sup>64<\/jats:sup>Cu]Cu-uPAR-PET\/CT was performed 1 h and 24 h after injection. After the last PET scan, all animals were euthanized, and tumors dissected for autoradiography and immunohistochemical (IHC) staining.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Three PDX models were established, and all of them showed histological stability and unchanged heterogenicity, uPAR expression, and Ki67 expression through passages. A significant correlation between uPAR expression and tumor growth was found. All tumors of all models (<jats:italic>n<\/jats:italic>=29) showed tumor uptake of [<jats:sup>64<\/jats:sup>Cu]Cu-DOTA-AE105. There was a clear visual concordance between the distribution of uPAR expression (IHC) and [<jats:sup>64<\/jats:sup>Cu]Cu-DOTA-AE105 uptake pattern in tumor tissue (autoradiography). No significant correlation was found between IHC (H-score) and PET-signal (SUV<jats:sub>max<\/jats:sub>) (<jats:italic>r<\/jats:italic>=0.34; <jats:italic>p<\/jats:italic>=0.07).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>OSCC PDX models in early passages histologically mimic donor tumors and could serve as a valuable platform for the development of uPAR-targeted imaging and therapeutic modalities. Furthermore, [64Cu]Cu-uPAR-PET\/CT showed target- and tumor-specific uptake in OSCC PDX models demonstrating the diagnostic potential of this modality for OSCC patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11307-023-01858-x","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T17:01:42Z","timestamp":1695661302000},"page":"1034-1044","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Urokinase-Type Plasminogen Activator Receptor (uPAR) Expression and [64Cu]Cu-DOTA-AE105 uPAR-PET\/CT in Patient-Derived Xenograft Models of Oral Squamous Cell Carcinoma"],"prefix":"10.1007","volume":"25","author":[{"given":"Mads","family":"Lawaetz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Binderup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Juhl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giedrius","family":"Lelkaitis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Lykke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Line","family":"Knudsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"von Buchwald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Kjaer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"1858_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/CAAC.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209\u2013249. https:\/\/doi.org\/10.3322\/CAAC.21660","journal-title":"CA Cancer J Clin"},{"key":"1858_CR2","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.oraloncology.2019.02.001","volume":"90","author":"DK Zanoni","year":"2019","unstructured":"Zanoni DK, Montero PH, Migliacci JC, Shah JP, Wong RJ, Ganly I, Patel SG (2019) Survival outcomes after treatment of cancer of the oral cavity (1985\u20132015). Oral Oncol 90:115\u2013121. https:\/\/doi.org\/10.1016\/j.oraloncology.2019.02.001","journal-title":"Oral Oncol"},{"key":"1858_CR3","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1470-2045(13)70546-1","volume":"15","author":"R De Angelis","year":"2014","unstructured":"De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, Trama A, Visser O, Brenner H, Ardanaz E et al (2014) Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE-5-a population-based study. Lancet Oncol 15:23\u201334. https:\/\/doi.org\/10.1016\/S1470-2045(13)70546-1","journal-title":"Lancet Oncol"},{"key":"1858_CR4","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1097\/00005537-200305000-00022","volume":"113","author":"JE Barrera","year":"2003","unstructured":"Barrera JE, Miller ME, Said S, Jafek BW, Campana JP, Shroyer KR (2003) Detection of occult cervical micrometastases in patients with head and neck squamous cell cancer. Laryngoscope 113:892\u2013896. https:\/\/doi.org\/10.1097\/00005537-200305000-00022","journal-title":"Laryngoscope"},{"key":"1858_CR5","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1016\/j.ejca.2015.08.023","volume":"51","author":"C Schilling","year":"2015","unstructured":"Schilling C, Stoeckli SJ, Haerle SK, Broglie MA, Huber GF, Sorensen JA, Bakholdt V, Krogdahl A, Von Buchwald C, Bilde A et al (2015) Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer. Eur J Cancer 51:2777\u20132784. https:\/\/doi.org\/10.1016\/j.ejca.2015.08.023","journal-title":"Eur J Cancer"},{"key":"1858_CR6","doi-asserted-by":"publisher","first-page":"3575","DOI":"10.1245\/s10434-013-3044-0","volume":"20","author":"M Amit","year":"2013","unstructured":"Amit M, Yen TC, Liao CT, Binenbaum Y, Chaturvedi P, Agarwal JP, Kowalski LP, Ebrahimi A, Clark JR, Cernea CR et al (2013) Clinical nodal stage is a significant predictor of outcome in patients with oral cavity squamous cell carcinoma and pathologically negative neck metastases: results of the international consortium for outcome research. Ann Surg Oncol 20:3575\u20133581. https:\/\/doi.org\/10.1245\/s10434-013-3044-0","journal-title":"Ann Surg Oncol"},{"key":"1858_CR7","doi-asserted-by":"publisher","first-page":"3185","DOI":"10.1002\/HED.26803","volume":"43","author":"Z Ding","year":"2021","unstructured":"Ding Z, Li Y, Pan X, Xuan M, Xie H, Wang X (2021) Sentinel lymph node biopsy versus elective neck dissection in squamous cell carcinoma of the oral cavity with a clinically n0 neck: systematic review and meta-analysis of prospective studies. Head Neck 43:3185\u20133198. https:\/\/doi.org\/10.1002\/HED.26803","journal-title":"Head Neck"},{"key":"1858_CR8","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1056\/nejmoa1506007","volume":"373","author":"AK D\u2019Cruz","year":"2015","unstructured":"D\u2019Cruz AK, Vaish R, Kapre N, Dandekar M, Gupta S, Hawaldar R, Agarwal JP, Pantvaidya G, Chaukar D, Deshmukh A et al (2015) Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med 373:521\u2013529. https:\/\/doi.org\/10.1056\/nejmoa1506007","journal-title":"N Engl J Med"},{"key":"1858_CR9","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1021\/mp500177c","volume":"11","author":"M Persson","year":"2014","unstructured":"Persson M, Juhl K, Rasmussen P, Brandt-Larsen M, Madsen J, Ploug M, Kjaer A (2014) UPAR targeted radionuclide therapy with 177Lu-DOTA-AE105 inhibits dissemination of metastatic prostate cancer. Mol Pharm 11:2796\u20132806. https:\/\/doi.org\/10.1021\/mp500177c","journal-title":"Mol Pharm"},{"key":"1858_CR10","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1007\/S00259-021-05559-X","volume":"49","author":"NG Quigley","year":"2022","unstructured":"Quigley NG, Steiger K, Hober\u00fcck S, Czech N, Zierke MA, Kossatz S, Pretze M, Richter F, Weichert W, Pox C et al (2022) PET\/CT imaging of head-and-neck and pancreatic cancer in humans by targeting the \u201ccancer integrin\u201d \u0391v\u03b26 with Ga-68-trivehexin. Eur J Nucl Med Mol Imaging 49:1136\u20131147. https:\/\/doi.org\/10.1007\/S00259-021-05559-X","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"1858_CR11","doi-asserted-by":"publisher","unstructured":"Durante S, Dunet V, Gorostidi F, Mitsakis P, Schaefer N, Delage J, Prior JO (2020) Head and neck tumors angiogenesis imaging with 68Ga-NODAGA-RGD in comparison to 18F-FDG PET\/CT: a pilot study. EJNMMI Res 10. https:\/\/doi.org\/10.1186\/S13550-020-00638-W","DOI":"10.1186\/S13550-020-00638-W"},{"key":"1858_CR12","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.radonc.2016.11.020","volume":"122","author":"J van Loon","year":"2017","unstructured":"van Loon J, Even AJG, Aerts HJWL, \u00d6llers M, Hoebers F, van Elmpt W, Dubois L, Dingemans AMC, Lalisang RI, Kempers P et al (2017) PET imaging of zirconium-89 labelled cetuximab: a phase I Trial in patients with head and neck and lung cancer. Radiother Oncol 122:267\u2013273. https:\/\/doi.org\/10.1016\/j.radonc.2016.11.020","journal-title":"Radiother Oncol"},{"key":"1858_CR13","doi-asserted-by":"publisher","first-page":"3110","DOI":"10.1158\/1078-0432.CCR-19-3484","volume":"26","author":"H Sch\u00f6der","year":"2020","unstructured":"Sch\u00f6der H, de Souza Fran\u00e7a PD, Nakajima R, Burnazi E, Roberts S, Brand C, Grkovski M, Mauguen A, Dunphy MP, Ghossein RA et al (2020) Safety and feasibility of PARP1\/2 imaging with 18F-PARPi in patients with head and neck cancer. Clin Cancer Res 26:3110\u20133116. https:\/\/doi.org\/10.1158\/1078-0432.CCR-19-3484","journal-title":"Clin Cancer Res"},{"key":"1858_CR14","doi-asserted-by":"publisher","first-page":"487","DOI":"10.7150\/thno.4218","volume":"3","author":"H Noh","year":"2013","unstructured":"Noh H, Hong S, Huang S (2013) Role of urokinase receptor in tumor progression and development. Theranostics 3:487\u2013495","journal-title":"Theranostics"},{"key":"1858_CR15","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.ctrv.2007.10.005","volume":"34","author":"K Dass","year":"2008","unstructured":"Dass K, Ahmad A, Azmi AS, Sarkar SH, Sarkar FH (2008) Evolving role of UPA\/UPAR system in human cancers. Cancer Treat Rev 34:122\u2013136. https:\/\/doi.org\/10.1016\/j.ctrv.2007.10.005","journal-title":"Cancer Treat Rev"},{"key":"1858_CR16","doi-asserted-by":"publisher","first-page":"3853","DOI":"10.3390\/IJMS24043853","volume":"24","author":"M Lawaetz","year":"2023","unstructured":"Lawaetz M, Christensen A, Juhl K, Karnov K, Lelkaitis G, Fiehn A-MK, Kjaer A, von Buchwald C (2023) Potential of UPAR, \u0391v\u03b26 integrin, and tissue factor as targets for molecular imaging of oral squamous cell carcinoma: evaluation of nine targets in primary tumors and metastases by immunohistochemistry. Int J Mol Sci 24:3853. https:\/\/doi.org\/10.3390\/IJMS24043853","journal-title":"Int J Mol Sci"},{"key":"1858_CR17","doi-asserted-by":"publisher","unstructured":"Christensen A, Kiss K, Lelkaitis G, Juhl K, Persson M, Charabi BW, Mortensen J, Forman JL, S\u00f8rensen AL, Jensen DH et al (2017) Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR): tumor expression patterns and prognostic value in oral cancer. BMC Cancer 17. https:\/\/doi.org\/10.1186\/s12885-017-3563-3","DOI":"10.1186\/s12885-017-3563-3"},{"key":"1858_CR18","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.2174\/138161211796718233","volume":"17","author":"MC Boonstra","year":"2011","unstructured":"Boonstra MC, Verspaget HW, Ganesh S, FJGM K, Vahrmeijer AL, CJH v d V, PJK K, PHA Q, CFM S (2011) Clinical applications of the urokinase receptor (UPAR) for cancer patients. Curr Pharm Des 17:1890\u20131910. https:\/\/doi.org\/10.2174\/138161211796718233","journal-title":"Curr Pharm Des"},{"key":"1858_CR19","doi-asserted-by":"publisher","first-page":"354","DOI":"10.2967\/JNUMED.120.248120","volume":"62","author":"M\u00d8 Fosb\u00f8l","year":"2021","unstructured":"Fosb\u00f8l M\u00d8, Kurbegovic S, Johannesen HH, R\u00f8der MA, Hansen AE, Mortensen J, Loft A, Petersen PM, Madsen J, Brasso K et al (2021) Urokinase-type plasminogen activator receptor (UPAR) PET\/MRI of prostate cancer for noninvasive evaluation of aggressiveness: comparison with gleason score in a prospective phase 2 clinical trial. J Nucl Med 62:354. https:\/\/doi.org\/10.2967\/JNUMED.120.248120","journal-title":"J Nucl Med"},{"issue":"9","key":"1858_CR20","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.2967\/JNUMED.121.263177","volume":"63","author":"EA Carlsen","year":"2022","unstructured":"Carlsen EA, Loft M, Loft A, Berthelsen AK, Langer SW, Knigge U, Kjaer A (2022) Prospective phase II trial of prognostication by 68Ga-NOTA-AE105 uPAR PET in patients with neuroendocrine neoplasms: implications for uPAR targeted therapy. J Nucl Med 63(9):1371\u20131377. https:\/\/doi.org\/10.2967\/JNUMED.121.263177","journal-title":"J Nucl Med"},{"issue":"8","key":"1858_CR21","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.2967\/jnumed.121.262866","volume":"63","author":"LM Ris\u00f8r","year":"2022","unstructured":"Ris\u00f8r LM, Clausen MM, Ujmajuridze Z, Farhadi M, Andersen KF, Loft A, Friborg J, Kjaer A (2022) Prognostic value of urokinase-type plasminogen activator receptor PET\/CT in head and neck squamous cell carcinomas and comparison with 18F-FDG-PET\/CT: a single-center prospective study. J Nucl Med 63(8):1169\u20131176. https:\/\/doi.org\/10.2967\/jnumed.121.262866","journal-title":"J Nucl Med"},{"key":"1858_CR22","doi-asserted-by":"publisher","first-page":"12157","DOI":"10.1021\/bi010662g","volume":"40","author":"M Ploug","year":"2001","unstructured":"Ploug M, \u00d8stergaard S, G\u00e5rdsvoll H, Kovalski K, Holst-Hansen C, Holm A, Ossowski L, Dan\u00f8 K (2001) Peptide-derived antagonists of the urokinase receptor. Affinity maturation by combinatorial chemistry, identification of functional epitopes, and inhibitory effect on cancer cell intravasation. Biochemistry 40:12157\u201312168. https:\/\/doi.org\/10.1021\/bi010662g","journal-title":"Biochemistry"},{"key":"1858_CR23","doi-asserted-by":"publisher","first-page":"451","DOI":"10.2967\/jnumed.116.180430","volume":"58","author":"CB Johnbeck","year":"2017","unstructured":"Johnbeck CB, Knigge U, Loft A, Berthelsen AK, Mortensen J, Oturai P, Langer SW, Elema DR, Kjaer A (2017) Head-to-head comparison of 64Cu-DOTATATE and 68Ga-DOTATOC PET\/CT: a prospective study of 59 patients with neuroendocrine tumors. J Nucl Med 58:451\u2013457. https:\/\/doi.org\/10.2967\/jnumed.116.180430","journal-title":"J Nucl Med"},{"key":"1858_CR24","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.7150\/THNO.12956","volume":"5","author":"M Persson","year":"2015","unstructured":"Persson M, Skovgaard D, Brandt-Larsen M, Christensen C, Madsen J, Nielsen CH, Thurison T, Klausen TL, Holm S, Loft A et al (2015) First-in-human UPAR PET: imaging of cancer aggressiveness. Theranostics 5:1303. https:\/\/doi.org\/10.7150\/THNO.12956","journal-title":"Theranostics"},{"key":"1858_CR25","doi-asserted-by":"publisher","first-page":"15407","DOI":"10.18632\/oncotarget.14282","volume":"8","author":"A Christensen","year":"2017","unstructured":"Christensen A, Juhl K, Persson M, Charabi BW, Mortensen J, Kiss K, Lelkaitis G, Rubek N, von Buchwald C, Kj\u00e6r A (2017) UPAR-targeted optical near-infrared (NIR) fluorescence imaging and PET for image-guided surgery in head and neck cancer: proof-of-concept in orthotopic xenograft model. Oncotarget 8:15407\u201315419. https:\/\/doi.org\/10.18632\/oncotarget.14282","journal-title":"Oncotarget"},{"key":"1858_CR26","doi-asserted-by":"publisher","unstructured":"Abdolahi S, Ghazvinian Z, Muhammadnejad S, Saleh M, Asadzadeh Aghdaei H, Baghaei K (2022) Patient-derived xenograft (PDX) models, applications and challenges in cancer research. J Transl Med 20. https:\/\/doi.org\/10.1186\/S12967-022-03405-8","DOI":"10.1186\/S12967-022-03405-8"},{"key":"1858_CR27","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.1093\/ANNONC\/MDX416","volume":"28","author":"E Izumchenko","year":"2017","unstructured":"Izumchenko E, Paz K, Ciznadija D, Sloma I, Katz A, Vasquez-Dunddel D, Ben-Zvi I, Stebbing J, McGuire W, Harris W et al (2017) Patient-derived xenografts effectively capture responses to oncology therapy in a heterogeneous cohort of patients with solid tumors. Ann Oncol 28:2595. https:\/\/doi.org\/10.1093\/ANNONC\/MDX416","journal-title":"Ann Oncol"},{"key":"1858_CR28","doi-asserted-by":"publisher","first-page":"5314","DOI":"10.1158\/1078-0432.CCR-12-0372\/85035\/AM\/CHARACTERIZATION-OF-A-LARGE-PANEL-OF-PATIENT","volume":"18","author":"S Julien","year":"2012","unstructured":"Julien S, Merino-Trigo A, Lacroix L, Pocard M, Goe\u0155\u00e9 D, Mariani P, Landron S, Bigot L, Nemati F, Dartigues P et al (2012) Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer. Clin Cancer Res 18:5314\u20135328. https:\/\/doi.org\/10.1158\/1078-0432.CCR-12-0372\/85035\/AM\/CHARACTERIZATION-OF-A-LARGE-PANEL-OF-PATIENT","journal-title":"Clin Cancer Res"},{"key":"1858_CR29","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1002\/ijc.24166","volume":"124","author":"M Illemann","year":"2009","unstructured":"Illemann M, Bird N, Majeed A, L\u00e6rum OD, Lund LR, Dan\u00f8 K, Nielsen BS (2009) Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases. Int J Cancer 124:1860\u20131870. https:\/\/doi.org\/10.1002\/ijc.24166","journal-title":"Int J Cancer"},{"key":"1858_CR30","doi-asserted-by":"publisher","first-page":"2559","DOI":"10.2174\/092986708785909012","volume":"15","author":"B Jacobsen","year":"2008","unstructured":"Jacobsen B, Ploug M (2008) The urokinase receptor and its structural homologue c4.4a in human cancer: expression, prognosis and pharmacological inhibition. Curr Med Chem 15:2559\u20132573. https:\/\/doi.org\/10.2174\/092986708785909012","journal-title":"Curr Med Chem"},{"issue":"23","key":"1858_CR31","doi-asserted-by":"publisher","first-page":"2275","DOI":"10.4161\/cbt.8.23.10137","volume":"8","author":"M Seshadri","year":"2009","unstructured":"Seshadri M, Merzianu M, Tang H, Rigual NR, Sullivan M, Loree TR, Popat SR, Repasky EA, Hylander BL (2009) Establishment and characterization of patient tumor-derived head and neck squamous cell carcinoma xenografts. Cancer Biol Ther 8(23):2275\u201383","journal-title":"Cancer Biol Ther"},{"key":"1858_CR32","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1158\/1078-0432.CCR-12-2746","volume":"19","author":"RJ Kimple","year":"2013","unstructured":"Kimple RJ, Harari PM, Torres AD, Yang RZ, Soriano BJ, Yu M, Armstrong EA, Blitzer GC, Smith MA, Lorenz LD et al (2013) Development and characterization of HPV-positive and HPV-negative head and neck squamous cell carcinoma tumorgrafts. Clin Cancer Res 19:855\u2013864. https:\/\/doi.org\/10.1158\/1078-0432.CCR-12-2746","journal-title":"Clin Cancer Res"},{"key":"1858_CR33","doi-asserted-by":"publisher","unstructured":"Peng S, Creighton CJ, Zhang Y, Sen B, Mazumdar T, Myers JN, Woolfson A, Lorenzi MV, Bell D, Williams MD et al (2013) Tumor grafts derived from patients with head and neck squamous carcinoma authentically maintain the molecular and histologic characteristics of human cancers. J Transl Med 11. https:\/\/doi.org\/10.1186\/1479-5876-11-198","DOI":"10.1186\/1479-5876-11-198"},{"issue":"2","key":"1858_CR34","doi-asserted-by":"publisher","first-page":"419","DOI":"10.3390\/cancers12020419","volume":"12","author":"PF Cosper","year":"2020","unstructured":"Cosper PF, Abel L, Lee YS, Paz C, Kaushik S, Nickel KP, Alexandridis R, Scott JG, Bruce JY, Kimple RJ (2020) Patient derived models to study head and neck cancer radiation response. Cancers (Basel) 12(2):419","journal-title":"Cancers (Basel)"},{"key":"1858_CR35","doi-asserted-by":"publisher","unstructured":"Kang HN, Kim JH, Park AY, Choi JW, Lim SM, Kim J, Shin EJ, Hong MH, Pyo KH, Yun MR et al (2020) Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer. BMC Cancer 20. https:\/\/doi.org\/10.1186\/s12885-020-06786-5","DOI":"10.1186\/s12885-020-06786-5"},{"key":"1858_CR36","doi-asserted-by":"publisher","unstructured":"Bankhead P, Loughrey MB, Fern\u00e1ndez JA, Dombrowski Y, McArt DG, Dunne PD, McQuaid S, Gray RT, Murray LJ, Coleman HG et al (2017) QuPath: open source software for digital pathology image analysis. Sci Rep 7. https:\/\/doi.org\/10.1038\/S41598-017-17204-5","DOI":"10.1038\/S41598-017-17204-5"},{"key":"1858_CR37","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/0046-8177(95)90060-8","volume":"26","author":"H Goulding","year":"1995","unstructured":"Goulding H, Pinder S, Cannon P, Pearson D, Nicholson R, Snead D, Bell J, Elston CWE, Robertson JF, Blamey RW et al (1995) A new immunohistochemical antibody for the assessment of estrogen receptor status on routine formalin-fixed tissue samples. Hum Pathol 26:291\u2013294. https:\/\/doi.org\/10.1016\/0046-8177(95)90060-8","journal-title":"Hum Pathol"},{"key":"1858_CR38","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/J.ORALONCOLOGY.2016.11.017","volume":"64","author":"AD Swick","year":"2017","unstructured":"Swick AD, Stein AP, McCulloch TM, Hartig GK, Ong IM, Sampene E, Prabakaran PJ, Liu CZ, Kimple RJ (2017) Defining the boundaries and expanding the utility of head and neck cancer patient derived xenografts. Oral Oncol 64:65. https:\/\/doi.org\/10.1016\/J.ORALONCOLOGY.2016.11.017","journal-title":"Oral Oncol"},{"key":"1858_CR39","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1016\/j.celrep.2018.07.058","volume":"24","author":"KM Campbell","year":"2018","unstructured":"Campbell KM, Lin T, Zolkind P, Barnell EK, Skidmore ZL, Winkler AE, Law JH, Mardis ER, Wartman LD, Adkins DR et al (2018) Oral cavity squamous cell carcinoma xenografts retain complex genotypes and intertumor molecular heterogeneity. Cell Rep. 24:2167\u20132178. https:\/\/doi.org\/10.1016\/j.celrep.2018.07.058","journal-title":"Cell Rep."},{"key":"1858_CR40","doi-asserted-by":"publisher","unstructured":"Makita H, Endo K, Kasahara Y, Nakata A, Moriyama-Kita M, Ishikawa K, Ueno T, Nakanishi Y, Kondo S, Wakisaka N et al (2021) Xenografts derived from patients with head and neck cancer recapitulate patient tumour properties. Oncol Lett 21. https:\/\/doi.org\/10.3892\/OL.2021.12646","DOI":"10.3892\/OL.2021.12646"},{"key":"1858_CR41","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.bcp.2014.06.008","volume":"91","author":"E Rosfjord","year":"2014","unstructured":"Rosfjord E, Lucas J, Li G, Gerber HP (2014) Advances in patient-derived tumor xenografts: from target identification to predicting clinical response rates in oncology. Biochem Pharmacol 91:135\u2013143","journal-title":"Biochem Pharmacol"},{"key":"1858_CR42","doi-asserted-by":"publisher","first-page":"4758","DOI":"10.1158\/1078-0432.CCR-07-4434","volume":"14","author":"ZB Li","year":"2008","unstructured":"Li ZB, Niu G, Wang H, He L, Yang L, Ploug M, Chen X (2008) Imaging of urokinase-type plasminogen activator receptor expression using a 64cu-labeled linear peptide antagonist by MicroPET. Clin Cancer Res 14:4758\u20134766. https:\/\/doi.org\/10.1158\/1078-0432.CCR-07-4434","journal-title":"Clin Cancer Res"},{"key":"1858_CR43","doi-asserted-by":"publisher","first-page":"138","DOI":"10.2967\/jnumed.110.083386","volume":"53","author":"M Persson","year":"2012","unstructured":"Persson M, Madsen J, \u00d8stergaard S, Jensen MM, J\u00f8rgensen JT, Juhl K, Lehmann C, Ploug M, Kjaer A (2012) Quantitative PET of human urokinase-type plasminogen activator receptor with 64Cu-DOTA-AE105: implications for visualizing cancer invasion. J Nucl Med 53:138\u2013145. https:\/\/doi.org\/10.2967\/jnumed.110.083386","journal-title":"J Nucl Med"},{"key":"1858_CR44","doi-asserted-by":"publisher","first-page":"618","DOI":"10.7150\/THNO.6810","volume":"3","author":"M Persson","year":"2013","unstructured":"Persson M, Hosseini M, Madsen J, J\u00f8rgensen TJD, Jensen KJ, Kjaer A, Ploug M (2013) Improved PET imaging of UPAR expression using new 64Cu-labeled cross-bridged peptide ligands: comparative in vitro and in vivo studies. Theranostics 3:618. https:\/\/doi.org\/10.7150\/THNO.6810","journal-title":"Theranostics"},{"key":"1858_CR45","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.nucmedbio.2013.12.007","volume":"41","author":"M Persson","year":"2014","unstructured":"Persson M, El Ali HH, Binderup T, Pfeifer A, Madsen J, Rasmussen P, Kjaer A (2014) Dosimetry of 64Cu-DOTA-AE105, a PET tracer for UPAR imaging. Nucl Med Biol 41:290\u2013295. https:\/\/doi.org\/10.1016\/j.nucmedbio.2013.12.007","journal-title":"Nucl Med Biol"},{"key":"1858_CR46","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1016\/j.nucmedbio.2012.05.007","volume":"39","author":"M Persson","year":"2012","unstructured":"Persson M, Rasmussen P, Madsen J, Ploug M, Kjaer A (2012) New peptide receptor radionuclide therapy of invasive cancer cells: in vivo studies using 177 Lu-DOTA-AE105 targeting UPAR in human colorectal cancer xenografts. Nucl Med Biol 39:962\u2013969. https:\/\/doi.org\/10.1016\/j.nucmedbio.2012.05.007","journal-title":"Nucl Med Biol"},{"key":"1858_CR47","doi-asserted-by":"publisher","unstructured":"Zhai BT, Tian H, Sun J, Zou JB, Zhang XF, Cheng JX, Shi YJ et al (2022) Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer. J Transl Med 20. https:\/\/doi.org\/10.1186\/s12967-022-03329-3","DOI":"10.1186\/s12967-022-03329-3"}],"container-title":["Molecular Imaging and Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11307-023-01858-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11307-023-01858-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11307-023-01858-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T18:10:19Z","timestamp":1702923019000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11307-023-01858-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,25]]},"references-count":47,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["1858"],"URL":"https:\/\/doi.org\/10.1007\/s11307-023-01858-x","relation":{},"ISSN":["1536-1632","1860-2002"],"issn-type":[{"value":"1536-1632","type":"print"},{"value":"1860-2002","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,25]]},"assertion":[{"value":"6 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Andreas Kjaer is a co-inventor on a patent for the uPAR-PET composition of matter (WO 2014086364) and co-founder of Curasight, which owns the intellectual property rights for the uPAR-PET technology. This project received funding from Candys Foundation, the European Union\u2019s Horizon 2020 research and innovation programme under grant agreements no. 670261 (ERC Advanced Grant) and 668532 (Click-It), the Lundbeck Foundation, the Novo Nordisk Foundation, the Innovation Fund Denmark, the Neuroendocrine Tumor Research Foundation, the Danish Cancer Society, Arvid Nilsson Foundation, the Neye Foundation, the Sygeforsikringen danmark, the Research Foundation of Rigshospitalet, the Danish National Research Foundation (grant 126) - PERSIMUNE, the Research Council of the Capital Region of Denmark, the Danish Health Authority, and the John and Birthe Meyer Foundation and Research Council for Independent Research. Andreas Kjaer is a Lundbeck Foundation Professor.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}