{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:19:30Z","timestamp":1793236770173,"version":"4.5.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Innsbruck and Medical University of Innsbruck"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Complete and minimally invasive cancer surgery remains challenging. Targeting the fibroblast activation protein (FAP) offers valuable opportunities for surgical planning, intraoperative guidance and improved resection outcomes. Herein, we developed the first dimeric, dual-modality FAP-targeted imaging agents and investigated the influence of different near-infrared cyanine-7 dyes on their final properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Four dual-modality ligands based on the Fusarinine C scaffold were synthesized. Their FAP specificity and retention were evaluated in cellular and xenograft tumor models. The most promising candidates were labelled with\n                      <jats:sup>67\/68<\/jats:sup>\n                      Ga and assessed\n                      <jats:italic>in vivo<\/jats:italic>\n                      at early time points by PET\/CT imaging and by comparative SPECT\/CT and NIR fluorescence imaging (FI) up to two days post-injection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Distinct fluorophore influences on the properties of the final compounds were identified. The introduction of the s775z dye demonstrated a beneficial effect on the cellular uptake and on the\n                      <jats:italic>in vivo<\/jats:italic>\n                      biodistribution profile as revealed by the greatest improvement in blood clearance and the least off-target accumulation in liver and kidneys when compared to the control and to the other candidates respectively.\n                      <jats:italic>Ex vivo<\/jats:italic>\n                      \u00a0experiments and\u00a0\n                      <jats:italic>in vivo<\/jats:italic>\n                      \u00a0PET\/CT, SPECT\/CT and FI studies in xenografted\u00a0mice confirmed these findings and demonstrated\u00a0sustained tumor uptake (&gt;\u20097% ID\/g and\u2009&gt;\u20095% ID\/g at 1\u00a0h\u00a0and 1\u00a0day p.i. respectively) for\n                      <jats:sup>67<\/jats:sup>\n                      Ga-s775z-FFAPi and\n                      <jats:sup>67<\/jats:sup>\n                      Ga-IRDye-FFAPi.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this study we introduced and evaluated novel dimeric FAP-targeting agents for dual-modality applications. In the preclinical setting, within the group of compounds investigated, two candidates enabled tumor visualization through PET, SPECT and optical imaging, providing satisfactory background contrast after a single administration and supporting their potential for preoperative nuclear imaging and subsequent fluorescence-guided surgery.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-025-07626-z","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T07:03:53Z","timestamp":1763535833000},"page":"2578-2591","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel dimeric dual-modality FAP-targeted agents with favorable tumor retention for image-guided surgery: a preclinical study"],"prefix":"10.1007","volume":"53","author":[{"given":"Giacomo","family":"Gariglio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hasen\u00f6hrl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Bendova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbyn\u011bk","family":"Nov\u00fd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Rangger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kummer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley D.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Matuszczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milos","family":"Petrik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-4036","authenticated-orcid":false,"given":"Clemens","family":"Decristoforo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"7626_CR1","doi-asserted-by":"crossref","DOI":"10.1038\/s41572-020-00224-3","volume":"6","author":"DE Johnson","year":"2020","unstructured":"Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6:92.","journal-title":"Nat Rev Dis Primers"},{"key":"7626_CR2","unstructured":"National Comprehensive Cancer Network. NCCN Guidelines for Patients: Mouth Cancers. In: NCCN Guidelines for Patients: Head and Neck Cancers. National Comprehensive Cancer Network; 2024. Available from: https:\/\/www.nccn.org\/patients\/guidelines\/content\/PDF\/hn-oral-patient.pdf. Accessed 30 Oct 2025."},{"key":"7626_CR3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1515\/iss-2023-0031","volume":"8","author":"J Kr\u00f6plin","year":"2024","unstructured":"Kr\u00f6plin J, Reppenhagen J-C. Best practices and future challenges in the treatment of oral cancer. Innovative Surgical Sciences. 2024;8:215\u201320.","journal-title":"Innovative Surgical Sciences"},{"key":"7626_CR4","first-page":"1","volume":"33","author":"P Castaldi","year":"2013","unstructured":"Castaldi P, Leccisotti L, Bussu F, Miccich\u00e8 F, Rufini V. Role of (18)F-FDG PET-CT in head and neck squamous cell carcinoma. Acta Otorhinolaryngol Ital. 2013;33:1\u20138.","journal-title":"Acta Otorhinolaryngol Ital"},{"key":"7626_CR5","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1158\/1078-0432.CCR-14-3284","volume":"21","author":"EL Rosenthal","year":"2015","unstructured":"Rosenthal EL, Warram JM, De Boer E, Chung TK, Korb ML, Brandwein-Gensler M, et al. Safety and tumor specificity of cetuximab-IRDye800 for surgical navigation in head and neck cancer. Clin Cancer Res. 2015;21:3658\u201366.","journal-title":"Clin Cancer Res"},{"key":"7626_CR6","doi-asserted-by":"crossref","first-page":"4744","DOI":"10.1158\/1078-0432.CCR-16-2968","volume":"23","author":"EL Rosenthal","year":"2017","unstructured":"Rosenthal EL, Moore LS, Tipirneni K, de Boer E, Stevens TM, Hartman YE, et al. Sensitivity and specificity of cetuximab-IRDye800CW to identify regional metastatic disease in head and neck cancer. Clin Cancer Res. 2017;23:4744\u201352.","journal-title":"Clin Cancer Res"},{"key":"7626_CR7","doi-asserted-by":"crossref","first-page":"758","DOI":"10.2967\/jnumed.118.222810","volume":"60","author":"S van Keulen","year":"2019","unstructured":"van Keulen S, Nishio N, Fakurnejad S, Birkeland A, Martin BA, Lu G, et al. The clinical application of fluorescence-guided surgery in head and neck cancer. J Nucl Med. 2019;60:758\u201363.","journal-title":"J Nucl Med"},{"key":"7626_CR8","doi-asserted-by":"crossref","first-page":"432","DOI":"10.3390\/ph15040432","volume":"15","author":"M Kubeil","year":"2022","unstructured":"Kubeil M, Mart\u00ednez IIS, Bachmann M, Kopka K, Tuck KL, Stephan H. Dual-labelling strategies for nuclear and fluorescence molecular imaging: current status and future perspectives. Pharmaceuticals. 2022;15:432.","journal-title":"Pharmaceuticals"},{"key":"7626_CR9","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.apsb.2018.03.010","volume":"8","author":"J Zhao","year":"2018","unstructured":"Zhao J, Chen J, Ma S, Liu Q, Huang L, Chen X, et al. Recent developments in multimodality fluorescence imaging probes. Acta Pharm Sin B. 2018;8:320\u201338.","journal-title":"Acta Pharm Sin B"},{"key":"7626_CR10","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.3892\/mmr.2015.3197","volume":"11","author":"F Zi","year":"2015","unstructured":"Zi F, He J, He D, Li Y, Yang L, Cai Z. Fibroblast activation protein \u03b1 in tumor microenvironment: recent progression and implications. Mol Med Rep. 2015;11:3203\u201311.","journal-title":"Mol Med Rep"},{"key":"7626_CR11","doi-asserted-by":"crossref","first-page":"801","DOI":"10.2967\/jnumed.119.227967","volume":"60","author":"C Kratochwil","year":"2019","unstructured":"Kratochwil C, Flechsig P, Lindner T, Abderrahim L, Altmann A, Mier W, et al. 68Ga-FAPI PET\/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med. 2019;60:801\u20135.","journal-title":"J Nucl Med"},{"key":"7626_CR12","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.2967\/jnumed.118.210443","volume":"59","author":"T Lindner","year":"2018","unstructured":"Lindner T, Loktev A, Altmann A, Giesel F, Kratochwil C, Debus J, et al. Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein. J Nucl Med. 2018;59:1415\u201322.","journal-title":"J Nucl Med"},{"key":"7626_CR13","volume":"20","author":"D Li","year":"2022","unstructured":"Li D, Li X, Zhao J, Tan F. Advances in nuclear medicine-based molecular imaging in head and neck squamous cell carcinoma. J Transl Med. 2022;20:358.","journal-title":"J Transl Med"},{"key":"7626_CR14","doi-asserted-by":"crossref","DOI":"10.1016\/j.prp.2023.155052","volume":"253","author":"M Mitha","year":"2024","unstructured":"Mitha M, Aden D, Zaheer S, Alvi Y. Role of tumor budding and fibrotic cancer stroma in head and neck squamous cell carcinoma. Pathol-Res Pract. 2024;253:155052.","journal-title":"Pathol-Res Pract"},{"key":"7626_CR15","doi-asserted-by":"crossref","DOI":"10.3390\/cancers16030587","volume":"16","author":"C Cacchi","year":"2024","unstructured":"Cacchi C, Fischer HJ, Wermker K, Rashad A, Jonigk DD, H\u00f6lzle F, et al. New tumor budding evaluation in head and neck squamous cell carcinomas. Cancers (Basel). 2024;16:587.","journal-title":"Cancers (Basel)"},{"key":"7626_CR16","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/his.14070","volume":"76","author":"MR Dourado","year":"2020","unstructured":"Dourado MR, Miwa KY, Hamada GB, Paranaiba LM, Sawazaki-Calone \u00cd, Domingueti CB, et al. Prognostication for oral squamous cell carcinoma patients based on the tumour\u2013stroma ratio and tumour budding. Histopathology. 2020;76:906\u201318.","journal-title":"Histopathology"},{"key":"7626_CR17","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.4c01232","author":"R Rizzo","year":"2025","unstructured":"Rizzo R, Capozza M, Conti L, Avalle L, Poli V, Terreno E. Novel FAP-targeted heptamethine cyanines for NIRF imaging applications. Mol Pharm. 2025. https:\/\/doi.org\/10.1021\/acs.molpharmaceut.4c01232.","journal-title":"Mol Pharm"},{"key":"7626_CR18","volume":"10","author":"J Roy","year":"2020","unstructured":"Roy J, Hettiarachchi SU, Kaake M, Mukkamala R, Low PS. Design and validation of fibroblast activation protein alpha targeted imaging and therapeutic agents. Theranostics. 2020;10:5778.","journal-title":"Theranostics"},{"key":"7626_CR19","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1021\/acs.jmedchem.0c02171","volume":"64","author":"SL Slania","year":"2021","unstructured":"Slania SL, Das D, Lisok A, Du Y, Jiang Z, Mease RC, et al. Imaging of fibroblast activation protein in cancer xenografts using novel (4-quinolinoyl)-glycyl-2-cyanopyrrolidine-based small molecules. J Med Chem. 2021;64:4059\u201370.","journal-title":"J Med Chem"},{"key":"7626_CR20","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-025-07093-6","author":"E Lin","year":"2025","unstructured":"Lin E, Song M, Wang B, Shi X, Zhao J, Fu L, et al. Fibroblast activation protein peptide-targeted NIR-I\/II fluorescence imaging for stable and functional detection of hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2025. https:\/\/doi.org\/10.1007\/s00259-025-07093-6.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"7626_CR21","volume":"11","author":"D Li","year":"2023","unstructured":"Li D, Li X, Li J, Wang Y, Tan F, Li X. Development of a fibroblast activation protein-targeted PET\/NIR dual-modality probe and its application in head and neck cancer. Front Bioeng Biotechnol. 2023;11:1291824.","journal-title":"Front Bioeng Biotechnol"},{"key":"7626_CR22","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1007\/s00259-024-06691-0","volume":"51","author":"X Zhao","year":"2024","unstructured":"Zhao X, Zhang G, Chen J, Li Z, Shi Y, Li G, et al. A rationally designed nuclei-targeting FAPI 04-based molecular probe with enhanced tumor uptake for PET\/CT and fluorescence imaging. Eur J Nucl Med Mol Imaging. 2024;51:1593\u2013604.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"7626_CR23","volume":"146","author":"X Zhang","year":"2024","unstructured":"Zhang X, Huang J, Gong F, Cai Z, Liu Y, Tang G, et al. Synthesis and preclinical evaluation of a novel PET\/fluorescence dual-modality probe targeting fibroblast activation protein. Bioorg Chem. 2024;146:107275.","journal-title":"Bioorg Chem"},{"key":"7626_CR24","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1021\/acs.bioconjchem.1c00503","volume":"33","author":"J Ariztia","year":"2022","unstructured":"Ariztia J, Solmont K, Moise NP, Specklin S, Heck MP, Lamande-Langle S, et al. PET\/fluorescence imaging: an overview of the chemical strategies to build dual imaging tools. Bioconjug Chem. 2022;33:24\u201352.","journal-title":"Bioconjug Chem"},{"key":"7626_CR25","doi-asserted-by":"crossref","unstructured":"Zhao L, Pang Y, Xu D, Chen J, Yu S, Ruan D, et al. Preclinical and pilot clinical evaluation of novel dual-modality pet\/fluorescence probes targeting FAP for accurate tumor margin delineation. Eur J Nucl Med Mol Imaging. 2025;1\u201312.","DOI":"10.1007\/s00259-025-07512-8"},{"key":"7626_CR26","doi-asserted-by":"crossref","DOI":"10.3390\/ph14121212","volume":"14","author":"S Ballal","year":"2021","unstructured":"Ballal S, Yadav MP, Moon ES, Kramer VS, Roesch F, Kumari S, et al. First-in-human results on the biodistribution, pharmacokinetics, and dosimetry of [177Lu] Lu-DOTA. SA. FAPi and [177Lu] Lu-DOTAGA. (SA. FAPi) 2. Pharmaceuticals. 2021;14:1212.","journal-title":"Pharmaceuticals"},{"key":"7626_CR27","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.2967\/jnumed.122.264036","volume":"63","author":"A Galbiati","year":"2022","unstructured":"Galbiati A, Zana A, Bocci M, Millul J, Elsayed A, Mock J, et al. A dimeric FAP-targeting small-molecule radioconjugate with high and prolonged tumor uptake. J Nucl Med. 2022;63:1852\u20138.","journal-title":"J Nucl Med"},{"key":"7626_CR28","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/nbt.2468","volume":"31","author":"HS Choi","year":"2013","unstructured":"Choi HS, Gibbs SL, Lee JH, Kim SH, Ashitate Y, Liu F, et al. Targeted zwitterionic near-infrared fluorophores for improved optical imaging. Nat Biotechnol. 2013;31:148\u201353.","journal-title":"Nat Biotechnol"},{"key":"7626_CR29","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cbpa.2021.01.009","volume":"63","author":"SM Usama","year":"2021","unstructured":"Usama SM, Thapaliya ER, Luciano MP, Schnermann MJ. Not so innocent: impact of fluorophore chemistry on the in vivo properties of bioconjugates. Curr Opin Chem Biol. 2021;63:38\u201345.","journal-title":"Curr Opin Chem Biol"},{"key":"7626_CR30","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2019.00510","volume":"10","author":"P Debie","year":"2019","unstructured":"Debie P, Hernot S. Emerging fluorescent molecular tracers to guide intra-operative surgical decision-making. Front Pharmacol. 2019;10:510.","journal-title":"Front Pharmacol"},{"key":"7626_CR31","doi-asserted-by":"crossref","first-page":"234","DOI":"10.2967\/jnumed.119.233064","volume":"61","author":"AW Hensbergen","year":"2020","unstructured":"Hensbergen AW, Buckle T, van Willigen DM, Schottelius M, Welling MM, van der Wijk FA, et al. Hybrid tracers based on cyanine backbones targeting prostate-specific membrane antigen: tuning pharmacokinetic properties and exploring dye\u2013protein interaction. J Nucl Med. 2020;61:234\u201341.","journal-title":"J Nucl Med"},{"key":"7626_CR32","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1021\/acs.bioconjchem.6b00093","volume":"27","author":"A Bunschoten","year":"2016","unstructured":"Bunschoten A, van Willigen DM, Buckle T, van den Berg NS, Welling MM, Spa SJ, et al. Tailoring fluorescent dyes to optimize a hybrid RGD-tracer. Bioconjug Chem. 2016;27:1253\u20138.","journal-title":"Bioconjug Chem"},{"key":"7626_CR33","doi-asserted-by":"crossref","first-page":"639","DOI":"10.2967\/jnumed.117.201293","volume":"59","author":"A-C Baranski","year":"2018","unstructured":"Baranski A-C, Sch\u00e4fer M, Bauder-W\u00fcst U, Roscher M, Schmidt J, Stenau E, et al. PSMA-11\u2013derived dual-labeled PSMA inhibitors for preoperative PET imaging and precise fluorescence-guided surgery of prostate cancer. J Nucl Med. 2018;59:639\u201345.","journal-title":"J Nucl Med"},{"issue":"6","key":"7626_CR34","doi-asserted-by":"crossref","first-page":"986","DOI":"10.2967\/jnumed.117.205575","volume":"59","author":"T Buckle","year":"2018","unstructured":"Buckle T, van Willigen DM, Spa SJ, Hensbergen AW, van der Wal S, de Korne CM, et al. Tracers for fluorescence-guided surgery: how elongation of the polymethine chain in cyanine dyes alters the pharmacokinetics of a dual-modality c [RGDyK] tracer. J Nucl Med. 2018;59(6):986\u201392.","journal-title":"J Nucl Med"},{"key":"7626_CR35","doi-asserted-by":"crossref","first-page":"30130","DOI":"10.1021\/acsomega.1c04991","volume":"6","author":"RS Gamage","year":"2021","unstructured":"Gamage RS, Li D-H, Schreiber CL, Smith BD. Comparison of cRGDfK peptide probes with appended shielded heptamethine cyanine dye (s775z) for near infrared fluorescence imaging of cancer. ACS Omega. 2021;6:30130\u20139.","journal-title":"ACS Omega"},{"key":"7626_CR36","doi-asserted-by":"crossref","first-page":"12252","DOI":"10.1002\/ange.202004449","volume":"132","author":"DH Li","year":"2020","unstructured":"Li DH, Schreiber CL, Smith BD. Sterically shielded heptamethine cyanine dyes for bioconjugation and high performance near-infrared fluorescence imaging. Angew Chem. 2020;132:12252\u20139.","journal-title":"Angew Chem"},{"key":"7626_CR37","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676\u201382.","journal-title":"Nat Methods"},{"key":"7626_CR38","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.0030128","volume":"3","author":"M Schrettl","year":"2007","unstructured":"Schrettl M, Bignell E, Kragl C, Sabiha Y, Loss O, Eisendle M, et al. Distinct roles for intra-and extracellular siderophores during Aspergillus fumigatus infection. PLoS Pathog. 2007;3:e128.","journal-title":"PLoS Pathog"},{"key":"7626_CR39","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.2967\/jnumed.120.242958","volume":"61","author":"J Toms","year":"2020","unstructured":"Toms J, Kogler J, Maschauer S, Daniel C, Schmidkonz C, Kuwert T, et al. Targeting fibroblast activation protein: radiosynthesis and preclinical evaluation of an 18F-labeled FAP inhibitor. J Nucl Med. 2020;61:1806\u201313.","journal-title":"J Nucl Med"},{"key":"7626_CR40","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13550-024-01191-6","volume":"14","author":"CD van der Heide","year":"2024","unstructured":"van der Heide CD, Campeiro JD, Ruigrok EA, van den Brink L, Ponnala S, Hillier SM, et al. In vitro and ex vivo evaluation of preclinical models for FAP-targeted theranostics: differences and relevance for radiotracer evaluation. EJNMMI Res. 2024;14:125.","journal-title":"EJNMMI Res"},{"key":"7626_CR41","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-23403-5","volume":"8","author":"RK Orosco","year":"2018","unstructured":"Orosco RK, Tapia VJ, Califano JA, Clary B, Cohen EE, Kane C, et al. Positive surgical margins in the 10 most common solid cancers. Sci Rep. 2018;8:5686.","journal-title":"Sci Rep"},{"key":"7626_CR42","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/3171794","author":"D Summer","year":"2018","unstructured":"Summer D, Rangger C, Klingler M, Laverman P, Franssen GM, Lechner BE, et al. Exploiting the concept of multivalency with 68Ga- and 89Zr-labelled fusarinine C-minigastrin bioconjugates for targeting CCK2R expression. Contrast Media Mol Imaging. 2018. https:\/\/doi.org\/10.1155\/2018\/3171794.","journal-title":"Contrast Media Mol Imaging"},{"key":"7626_CR43","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.5b00128","author":"C Zhai","year":"2015","unstructured":"Zhai C, Summer D, Rangger C, Franssen GM, Laverman P, Haas H, et al. Novel bifunctional cyclic chelator for 89Zr labeling-radiolabeling and targeting properties of RGD conjugates. Mol Pharm. 2015. https:\/\/doi.org\/10.1021\/acs.molpharmaceut.5b00128.","journal-title":"Mol Pharm"},{"key":"7626_CR44","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1021\/acs.bioconjchem.7b00182","volume":"28","author":"D Summer","year":"2017","unstructured":"Summer D, Grossrubatscher L, Petrik M, Michalcikova T, Novy Z, Rangger C, et al. Developing targeted hybrid imaging probes by chelator scaffolding. Bioconjug Chem. 2017;28:1722\u201333.","journal-title":"Bioconjug Chem"},{"key":"7626_CR45","doi-asserted-by":"crossref","DOI":"10.3390\/ph17121569","volume":"17","author":"G Gariglio","year":"2024","unstructured":"Gariglio G, Bendova K, Hermann M, Olafsdottir A, Sosabowski JK, Petrik M, et al. Comparison of two chelator scaffolds as basis for cholecystokinin-2 receptor targeting bimodal imaging probes. Pharmaceuticals. 2024;17:1569.","journal-title":"Pharmaceuticals"},{"key":"7626_CR46","doi-asserted-by":"crossref","first-page":"58762","DOI":"10.1039\/C4RA11225C","volume":"4","author":"H Hyun","year":"2014","unstructured":"Hyun H, Owens EA, Narayana L, Wada H, Gravier J, Bao K, et al. Central c-c bonding increases optical and chemical stability of NIR fluorophores. RSC Adv. 2014;4:58762\u20138.","journal-title":"RSC Adv"},{"key":"7626_CR47","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1039\/C4CC08814J","volume":"51","author":"D Su","year":"2015","unstructured":"Su D, Teoh CL, Samanta A, Kang N-Y, Park S-J, Chang Y-T. The development of a highly photostable and chemically stable zwitterionic near-infrared dye for imaging applications. Chem Commun. 2015;51:3989\u201392.","journal-title":"Chem Commun"},{"key":"7626_CR48","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.7150\/thno.52166","volume":"11","author":"YH Derks","year":"2021","unstructured":"Derks YH, Rijpkema M, Amatdjais-Groenen HI, Kip A, Franssen GM, Sedelaar JM, et al. Photosensitizer-based multimodal PSMA-targeting ligands for intraoperative detection of prostate cancer. Theranostics. 2021;11:1527.","journal-title":"Theranostics"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-025-07626-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-025-07626-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-025-07626-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:39:04Z","timestamp":1771479544000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-025-07626-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,19]]},"references-count":48,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["7626"],"URL":"https:\/\/doi.org\/10.1007\/s00259-025-07626-z","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,19]]},"assertion":[{"value":"2 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The article was modified to correct the corrupted supplementary file.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experiments were performed in accordance with the regulations and guidelines of the Austrian and Czech Animal Protection Act and with the approval of the Austrian Ministry of Education, Science and Research (BMWFW-2023\u20130.037.240) and of the Czech Ministry of Education, Youth, and Sports (MSMT-24421\/2021\u20134 and MSMT-41830\/2018\u20137), and the institutional Animal Welfare Committee of the Faculty of Medicine and Dentistry of Palacky University in Olomouc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare the following competing financial interest: G. Gariglio, C. Rangger, M. Petrik and C. Decristoforo are involved in the patent application EP 25162629.7, entitled \u201cFAP-Targeted Dual Imaging for Guided Surgical Resection.\u201d B. D. Smith is listed as inventor of the patent US20230219933A1, entitled \u201cSterically Shielded Heptamethine Cyanine Dyes\u201d. The other authors declare no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}}]}}