{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T16:17:52Z","timestamp":1777047472478,"version":"3.51.4"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007797","name":"University of Helsinki","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007797","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EJNMMI radiopharm. chem."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The development of safer and more effective cell-based therapies requires robust methods for tracking cells in vivo. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique capable of quantitatively tracking the in vivo fate of cells after administration. Here, we investigated a cell-labeling strategy based on metabolic glycoengineering (MGE) to introduce azides on the cell surface, followed by radiolabeling via the bioorthogonal perfluoroaryl azide (PFAA)-Staudinger reaction. We studied the metabolic incorporation of a tetraacetylated PFAA-derivatized mannosamine in Jurkat cells and evaluated whether three triarylphosphines bearing the REstrained Complexing Agent (RESCA), could be radiolabeled with aluminum-[F]fluoride (Al[\n                      <jats:sup>18<\/jats:sup>\n                      F]F) for use as bioorthogonal reagents in the PFAA-Staudinger ligation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three novel triarylphosphines containing different linkers (hydrophilic ester, ethylenediamine, and cyclohexyl) between the phosphine moiety and the (+)-RESCA-chelator were synthesized and characterized. Kinetic assays showed that all compounds reacted with the PFAA-derivatized monosaccharide, exhibiting different reaction kinetics under the tested conditions. They were successfully radiolabeled with fluorine-18 under optimized mild conditions and provided key insights into the radiolabeling of small molecules bearing the RESCA-chelator. The ester derivative underwent rapid chemical decomposition while the ethylenediamine- and cyclohexyl-linked derivatives were more resistant, with the cyclohexyl analogue showing the highest stability against demetallation and\/or defluorination. However, radiolabeling with Al[\n                      <jats:sup>18<\/jats:sup>\n                      F]F led to the oxidation of the phosphine moiety, with the major radiolabeled product corresponding to the oxidized form. At the same time, flow cytometry showed that the metabolic incorporation of the tetra-acetylated PFAA-derivatized mannosamine into Jurkat cells was substantially less efficient than that of the widely used tetra-acetylated\n                      <jats:italic>N<\/jats:italic>\n                      -azidoacetylmannosamine (Ac\n                      <jats:sub>4<\/jats:sub>\n                      ManNAz) derivative at the equivalent concentration. Increased concentrations of the PFAA derivative compromised cell viability, which halted subsequent studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      While the Al[\n                      <jats:sup>18<\/jats:sup>\n                      F]F radiolabeling of these (+)-RESCA-bearing small molecules offers high stability against demetallation and\/or defluorination, the method cannot currently be applied to triarylphosphines due to oxidation during radiolabeling and requires further development. Among the synthesized compounds, the cyclohexyl-linked derivative exhibited the most favorable stability profile, making it a potential lead structure for future tracer development. Nevertheless, this study advanced our understanding of MGE with PFAA-derivatized monosaccharides and highlighted the need for further investigation before applying PFAA-Staudinger ligation to cell radiolabeling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s41181-025-00409-9","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T13:17:26Z","timestamp":1765286246000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aluminum-[18F]fluoride radiolabeling of triarylphosphines for cell labeling via the perfluoroaryl azide Staudinger ligation"],"prefix":"10.1186","volume":"10","author":[{"given":"Anisa","family":"Biti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surachet","family":"Imlimthan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Harjunp\u00e4\u00e4","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Barakhtii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Topias","family":"P\u00f6ll\u00e4nen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arina","family":"Sukhova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne K.","family":"Wiedmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filip S.","family":"Ekholm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Fagerholm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-4366","authenticated-orcid":false,"given":"Mirkka","family":"Sarparanta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"409_CR1","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1002\/bit.24363","volume":"109","author":"RT Almaraz","year":"2012","unstructured":"Almaraz RT, Aich U, Khanna HS, Tan E, Bhattacharya R, Shah S, et al. Metabolic oligosaccharide engineering with N-acyl functionalized ManNAc analogs: cytotoxicity, metabolic flux, and glycan-display considerations. Biotechnol Bioeng. 2012;109:992\u20131006. https:\/\/doi.org\/10.1002\/bit.24363.","journal-title":"Biotechnol Bioeng"},{"key":"409_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062820","volume":"22","author":"S Altmann","year":"2021","unstructured":"Altmann S, Mut J, Wolf N, Mei\u00dfner-Weigl J, Rudert M, Jakob F, et al. Metabolic glycoengineering in hMSC-TERT as a model for skeletal precursors by using modified azide\/alkyne monosaccharides. Int J Mol Sci. 2021;22:2820. https:\/\/doi.org\/10.3390\/ijms22062820.","journal-title":"Int J Mol Sci"},{"key":"409_CR3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s41181-021-00141-0","volume":"6","author":"SJ Archibald","year":"2021","unstructured":"Archibald SJ, Allott L. The aluminium-[18F]fluoride revolution: simple radiochemistry with a big impact for radiolabelled biomolecules. EJNMMI Radiopharm Chem. 2021;6:30. https:\/\/doi.org\/10.1186\/s41181-021-00141-0.","journal-title":"EJNMMI Radiopharm Chem"},{"key":"409_CR4","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.1021\/acs.bioconjchem.1c00461","volume":"32","author":"RE Bird","year":"2021","unstructured":"Bird RE, Lemmel SA, Yu X, Zhou QA. Bioorthogonal chemistry and its applications. Bioconjug Chem. 2021;32:2457\u201379. https:\/\/doi.org\/10.1021\/acs.bioconjchem.1c00461.","journal-title":"Bioconjug Chem"},{"key":"409_CR5","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1039\/C0OB00564A","volume":"9","author":"L Carroll","year":"2011","unstructured":"Carroll L, Boldon S, Bejot R, Moore JE, Declerck J, Gouverneur V. The traceless Staudinger ligation for indirect 18F-radiolabelling. Org Biomol Chem. 2011;9:136\u201340. https:\/\/doi.org\/10.1039\/C0OB00564A.","journal-title":"Org Biomol Chem"},{"key":"409_CR6","doi-asserted-by":"publisher","first-page":"8400","DOI":"10.1021\/ja070238o","volume":"129","author":"PV Chang","year":"2007","unstructured":"Chang PV, Prescher JA, Hangauer MJ, Bertozzi CR. Imaging cell surface glycans with bioorthogonal chemical reporters. J Am Chem Soc. 2007;129:8400\u20131. https:\/\/doi.org\/10.1021\/ja070238o.","journal-title":"J Am Chem Soc"},{"key":"409_CR7","doi-asserted-by":"publisher","first-page":"2859","DOI":"10.1007\/s10967-022-08359-1","volume":"331","author":"K Chen","year":"2022","unstructured":"Chen K, Zhang X, Wang F, Wu Y, Zhou H, Zhang Y, et al. Aluminum fluoride-18-labelled indocyanine green as a potential PET imaging agent for hepatic function reserve. J Radioanal Nucl Chem. 2022;331:2859\u201368. https:\/\/doi.org\/10.1007\/s10967-022-08359-1.","journal-title":"J Radioanal Nucl Chem"},{"key":"409_CR8","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1021\/acs.bioconjchem.6b00012","volume":"27","author":"F Cleeren","year":"2016","unstructured":"Cleeren F, Lecina J, Billaud EMF, Ahamed M, Verbruggen A, Bormans GM. New chelators for low temperature Al18F-labeling of biomolecules. Bioconjug Chem. 2016;27:790\u20138. https:\/\/doi.org\/10.1021\/acs.bioconjchem.6b00012.","journal-title":"Bioconjug Chem"},{"key":"409_CR9","doi-asserted-by":"publisher","first-page":"2924","DOI":"10.7150\/thno.20094","volume":"7","author":"F Cleeren","year":"2017","unstructured":"Cleeren F, Lecina J, Ahamed M, Raes G, Devoogdt N, Caveliers V, et al. Al18F-labeling of heat-sensitive biomolecules for positron emission tomography imaging. Theranostics. 2017;7:2924\u201339. https:\/\/doi.org\/10.7150\/thno.20094.","journal-title":"Theranostics"},{"key":"409_CR10","doi-asserted-by":"publisher","first-page":"2330","DOI":"10.1038\/s41596-018-0040-7","volume":"13","author":"F Cleeren","year":"2018","unstructured":"Cleeren F, Lecina J, Bridoux J, Devoogdt N, Tshibangu T, Xavier C, et al. Direct fluorine-18 labeling of heat-sensitive biomolecules for positron emission tomography imaging using the Al18F-RESCA method. Nat Protoc. 2018;13:2330\u201347. https:\/\/doi.org\/10.1038\/s41596-018-0040-7.","journal-title":"Nat Protoc"},{"key":"409_CR11","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1002\/cbic.201200719","volume":"14","author":"CM Cole","year":"2013","unstructured":"Cole CM, Yang J, \u0160e\u010dkut\u0117 J, Devaraj NK. Fluorescent live-cell imaging of metabolically incorporated unnatural cyclopropene-mannosamine derivatives. ChemBioChem. 2013;14:205\u20138. https:\/\/doi.org\/10.1002\/cbic.201200719.","journal-title":"ChemBioChem"},{"key":"409_CR12","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1021\/bc200175c","volume":"22","author":"CA D\u2019Souza","year":"2011","unstructured":"D\u2019Souza CA, McBride WJ, Sharkey RM, Todaro LJ, Goldenberg DM. High-yielding aqueous 18F-labeling of peptides via Al18F chelation. Bioconjug Chem. 2011;22:1793\u2013803. https:\/\/doi.org\/10.1021\/bc200175c.","journal-title":"Bioconjug Chem"},{"key":"409_CR13","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1002\/cbic.201000064","volume":"11","author":"MF Debets","year":"2010","unstructured":"Debets MF, van der Doelen CWJ, Rutjes FPJT, van Delft FL. Azide: a unique dipole for metal-free bioorthogonal ligations. ChemBioChem. 2010;11:1168\u201384. https:\/\/doi.org\/10.1002\/cbic.201000064.","journal-title":"ChemBioChem"},{"key":"409_CR14","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1093\/glycob\/cwp115","volume":"19","author":"J Du","year":"2009","unstructured":"Du J, Meledeo MA, Wang Z, Khanna HS, Paruchuri VDP, Yarema KJ. Metabolic glycoengineering: sialic acid and beyond. Glycobiology. 2009;19:1382\u2013401. https:\/\/doi.org\/10.1093\/glycob\/cwp115.","journal-title":"Glycobiology"},{"key":"409_CR15","doi-asserted-by":"publisher","first-page":"5049","DOI":"10.1038\/s41467-023-40886-7","volume":"14","author":"J Han","year":"2023","unstructured":"Han J, Bhatta R, Liu Y, Bo Y, Elosegui-Artola A, Wang H. Metabolic glycan labeling immobilizes dendritic cell membrane and enhances antitumor efficacy of dendritic cell vaccine. Nat Commun. 2023;14:5049. https:\/\/doi.org\/10.1038\/s41467-023-40886-7.","journal-title":"Nat Commun"},{"key":"409_CR16","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1002\/anie.200704847","volume":"47","author":"MJ Hangauer","year":"2008","unstructured":"Hangauer MJ, Bertozzi CR. A FRET-based fluorogenic phosphine for live-cell imaging with the Staudinger ligation. Angew Chem Int Ed Engl. 2008;47:2394\u20137. https:\/\/doi.org\/10.1002\/anie.200704847.","journal-title":"Angew Chem Int Ed Engl"},{"key":"409_CR17","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.nucmedbio.2020.11.003","volume":"93","author":"MM Herth","year":"2021","unstructured":"Herth MM, Ametamey S, Antuganov D, Bauman A, Berndt M, Brooks AF, et al. On the consensus nomenclature rules for radiopharmaceutical chemistry\u2014reconsideration of radiochemical conversion. Nucl Med Biol. 2021;93:19\u201321. https:\/\/doi.org\/10.1016\/j.nucmedbio.2020.11.003.","journal-title":"Nucl Med Biol"},{"key":"409_CR18","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s41181-024-00280-0","volume":"9","author":"MN Iannone","year":"2024","unstructured":"Iannone MN, Valtorta S, Stucchi S, Altomonte S, Turolla EA, Vino E, et al. Automated radiosynthesis and preclinical evaluation of two new PSMA-617 derivatives radiolabelled via [18F]AlF2+ method. EJNMMI Radiopharm Chem. 2024;9:50. https:\/\/doi.org\/10.1186\/s41181-024-00280-0.","journal-title":"EJNMMI Radiopharm Chem"},{"key":"409_CR19","doi-asserted-by":"publisher","first-page":"18342","DOI":"10.1074\/jbc.M400205200","volume":"279","author":"EJ Kim","year":"2004","unstructured":"Kim EJ, Sampathkumar S-G, Jones MB, Rhee JK, Baskaran G, Goon S, et al. Characterization of the metabolic flux and apoptotic effects of O-hydroxyl- and N-acyl-modified N-acetylmannosamine analogs in Jurkat cells*. J Biol Chem. 2004;279:18342\u201352. https:\/\/doi.org\/10.1074\/jbc.M400205200.","journal-title":"J Biol Chem"},{"key":"409_CR20","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.jconrel.2020.12.002","volume":"329","author":"W Kim","year":"2021","unstructured":"Kim W, Yoon HY, Lim S, Stayton PS, Kim I-S, Kim K, et al. In vivo tracking of bioorthogonally labeled T-cells for predicting therapeutic efficacy of adoptive T-cell therapy. J Control Release. 2021;329:223\u201336. https:\/\/doi.org\/10.1016\/j.jconrel.2020.12.002.","journal-title":"J Control Release"},{"key":"409_CR21","doi-asserted-by":"publisher","first-page":"11836","DOI":"10.1002\/anie.201206703","volume":"51","author":"H Koo","year":"2012","unstructured":"Koo H, Lee S, Na JH, Kim SH, Hahn SK, Choi K, et al. Bioorthogonal copper-free click chemistry in vivo for tumor-targeted delivery of nanoparticles. Angew Chem Int Ed Engl. 2012;51:11836\u201340. https:\/\/doi.org\/10.1002\/anie.201206703.","journal-title":"Angew Chem Int Ed Engl"},{"key":"409_CR22","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s41181-025-00359-2","volume":"10","author":"F Krutzek","year":"2025","unstructured":"Krutzek F, Donat CK, Stadlbauer S. Structure\u2013activity relationship of 18F-labeled PD-L1-targeting small molecule ligands: impact of radiolabeling strategy on affinity and in vivo performance. EJNMMI Radiopharm Chem. 2025;10:33. https:\/\/doi.org\/10.1186\/s41181-025-00359-2.","journal-title":"EJNMMI Radiopharm Chem"},{"key":"409_CR23","first-page":"230","volume-title":"Metabolic labeling of glycans with azido sugars for visualization and glycoproteomics. Methods in enzymology","author":"ST Laughlin","year":"2006","unstructured":"Laughlin ST, Agard NJ, Baskin JM, Carrico IS, Chang PV, Ganguli AS, et al. Metabolic labeling of glycans with azido sugars for visualization and glycoproteomics. Methods in enzymology. Academic Press; 2006. p. 230\u201350."},{"key":"409_CR24","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s41181-024-00304-9","volume":"9","author":"F Lechi","year":"2024","unstructured":"Lechi F, Eriksson J, Odell LR, Wegrzyniak O, L\u00f6fblom J, Frejd FY, et al. Optimized method for fluorine-18 radiolabeling of Affibody molecules using RESCA. EJNMMI Radiopharm Chem. 2024;9:73. https:\/\/doi.org\/10.1186\/s41181-024-00304-9.","journal-title":"EJNMMI Radiopharm Chem"},{"key":"409_CR25","doi-asserted-by":"publisher","first-page":"1804383","DOI":"10.1002\/smll.201804383","volume":"15","author":"W Li","year":"2019","unstructured":"Li W, Pan H, He H, Meng X, Ren Q, Gong P, et al. Bio-orthogonal T cell targeting strategy for robustly enhancing cytotoxicity against tumor cells. Small. 2019;15:1804383. https:\/\/doi.org\/10.1002\/smll.201804383.","journal-title":"Small"},{"key":"409_CR26","doi-asserted-by":"publisher","DOI":"10.1002\/biot.202300339","volume":"19","author":"X Li","year":"2024","unstructured":"Li X, Weller S, Clergeaud G, Andresen TL. A versatile method for conjugating lipid nanoparticles on T cells through combination of click chemistry and metabolic glycoengineering. Biotechnol J. 2024;19:2300339. https:\/\/doi.org\/10.1002\/biot.202300339.","journal-title":"Biotechnol J"},{"key":"409_CR27","doi-asserted-by":"publisher","first-page":"2686","DOI":"10.1021\/ja044461m","volume":"127","author":"FL Lin","year":"2005","unstructured":"Lin FL, Hoyt HM, van Halbeek H, Bergman RG, Bertozzi CR. Mechanistic investigation of the Staudinger ligation. J Am Chem Soc. 2005;127:2686\u201395. https:\/\/doi.org\/10.1021\/ja044461m.","journal-title":"J Am Chem Soc"},{"key":"409_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2023.144127","volume":"470","author":"Y Long","year":"2023","unstructured":"Long Y, Wei N, Yuan P, Lv X, Song X, Zhu Z, et al. NIRF\/PET imaging of \u03b3\u03b4 T cells via metabolic glycoengineering and bioorthogonal labeling. Chem Eng J. 2023;470:144127. https:\/\/doi.org\/10.1016\/j.cej.2023.144127.","journal-title":"Chem Eng J"},{"key":"409_CR29","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s12951-021-00924-2","volume":"19","author":"D Lu","year":"2021","unstructured":"Lu D, Wang Y, Zhang T, Wang F, Li K, Zhou S, et al. Metabolic radiolabeling and in vivo PET imaging of cytotoxic T lymphocytes to guide combination adoptive cell transfer cancer therapy. J Nanobiotechnology. 2021;19:175. https:\/\/doi.org\/10.1186\/s12951-021-00924-2.","journal-title":"J Nanobiotechnology"},{"key":"409_CR30","first-page":"249","volume-title":"Constructing Azide-labeled cell surfaces using polysaccharide biosynthetic pathways. Methods in enzymology","author":"SJ Luchansky","year":"2003","unstructured":"Luchansky SJ, Hang HC, Saxon E, Grunwell JR, Yu C, Dube DH, et al. Constructing Azide-labeled cell surfaces using polysaccharide biosynthetic pathways. Methods in enzymology. Academic Press; 2003. p. 249\u201372."},{"key":"409_CR31","doi-asserted-by":"publisher","first-page":"4521","DOI":"10.1016\/j.tet.2011.04.091","volume":"67","author":"C Mamat","year":"2011","unstructured":"Mamat C, Franke M, Peppel T, K\u00f6ckerling M, Steinbach J. Synthesis, structure determination, and (radio-)fluorination of novel functionalized phosphanes suitable for the traceless Staudinger ligation. Tetrahedron. 2011;67:4521\u20139. https:\/\/doi.org\/10.1016\/j.tet.2011.04.091.","journal-title":"Tetrahedron"},{"key":"409_CR32","doi-asserted-by":"publisher","first-page":"6629","DOI":"10.3390\/molecules26216629","volume":"26","author":"C Mamat","year":"2021","unstructured":"Mamat C, Jentschel C, K\u00f6ckerling M, Steinbach J. Strategic evaluation of the traceless staudinger ligation for radiolabeling with the tricarbonyl core. Molecules. 2021;26:6629. https:\/\/doi.org\/10.3390\/molecules26216629.","journal-title":"Molecules"},{"key":"409_CR33","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/2191-219X-3-36","volume":"3","author":"WJ McBride","year":"2013","unstructured":"McBride WJ, Sharkey RM, Goldenberg DM. Radiofluorination using aluminum-fluoride (Al18F). EJNMMI Res. 2013;3:36. https:\/\/doi.org\/10.1186\/2191-219X-3-36.","journal-title":"EJNMMI Res"},{"key":"409_CR34","doi-asserted-by":"publisher","first-page":"15096","DOI":"10.1021\/ja066779f","volume":"128","author":"TL Mindt","year":"2006","unstructured":"Mindt TL, Struthers H, Brans L, Anguelov T, Schweinsberg C, Maes V, et al. \u201cClick to chelate\u201d: synthesis and installation of metal chelates into biomolecules in a single step. J Am Chem Soc. 2006;128:15096\u20137. https:\/\/doi.org\/10.1021\/ja066779f.","journal-title":"J Am Chem Soc"},{"key":"409_CR35","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202203942","volume":"29","author":"MMA Mitry","year":"2023","unstructured":"Mitry MMA, Greco F, Osborn HMI. In vivo applications of bioorthogonal reactions: chemistry and targeting mechanisms. Chem Eur J. 2023;29:e202203942. https:\/\/doi.org\/10.1002\/chem.202203942.","journal-title":"Chem Eur J"},{"key":"409_CR36","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1021\/ol0060174","volume":"2","author":"BL Nilsson","year":"2000","unstructured":"Nilsson BL, Kiessling LL, Raines RT. Staudinger ligation: a peptide from a thioester and azide. Org Lett. 2000;2:1939\u201341. https:\/\/doi.org\/10.1021\/ol0060174.","journal-title":"Org Lett"},{"key":"409_CR37","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/nchembio0605-13","volume":"1","author":"JA Prescher","year":"2005","unstructured":"Prescher JA, Bertozzi CR. Chemistry in living systems. Nat Chem Biol. 2005;1:13\u201321. https:\/\/doi.org\/10.1038\/nchembio0605-13.","journal-title":"Nat Chem Biol"},{"key":"409_CR38","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1038\/nature02791","volume":"430","author":"JA Prescher","year":"2004","unstructured":"Prescher JA, Dube DH, Bertozzi CR. Chemical remodelling of cell surfaces in living animals. Nature. 2004;430:873\u20137. https:\/\/doi.org\/10.1038\/nature02791.","journal-title":"Nature"},{"key":"409_CR39","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1515\/znb-2010-0912","volume":"65","author":"M Pretze","year":"2010","unstructured":"Pretze M, Flemming A, Kockerling M, Mamat C. Synthesis and radiofluorination of iodophenyl esters as tool for the traceless Staudinger ligation. Z Naturforsch B. 2010a;65:1128\u201336. https:\/\/doi.org\/10.1515\/znb-2010-0912.","journal-title":"Z Naturforsch B"},{"key":"409_CR40","doi-asserted-by":"publisher","first-page":"6410","DOI":"10.1016\/j.tetlet.2010.09.134","volume":"51","author":"M Pretze","year":"2010","unstructured":"Pretze M, Wuest F, Peppel T, K\u00f6ckerling M, Mamat C. The traceless staudinger ligation with fluorine-18: a novel and versatile labeling technique for the synthesis of PET-radiotracers. Tetrahedron Lett. 2010b;51:6410\u20134. https:\/\/doi.org\/10.1016\/j.tetlet.2010.09.134.","journal-title":"Tetrahedron Lett"},{"key":"409_CR41","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1039\/C3CS60304K","volume":"43","author":"EW Price","year":"2014","unstructured":"Price EW, Orvig C. Matching chelators to radiometals for radiopharmaceuticals. Chem Soc Rev. 2014;43:260\u201390. https:\/\/doi.org\/10.1039\/C3CS60304K.","journal-title":"Chem Soc Rev"},{"key":"409_CR42","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.1126\/science.287.5460.2007","volume":"287","author":"E Saxon","year":"2000","unstructured":"Saxon E, Bertozzi CR. Cell surface engineering by a modified Staudinger reaction. Science. 2000;287:2007\u201310. https:\/\/doi.org\/10.1126\/science.287.5460.2007.","journal-title":"Science"},{"key":"409_CR43","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1021\/ol006054v","volume":"2","author":"E Saxon","year":"2000","unstructured":"Saxon E, Armstrong JI, Bertozzi CR. A \u201ctraceless\u201d Staudinger ligation for the chemoselective synthesis of amide bonds. Org Lett. 2000;2:2141\u20133. https:\/\/doi.org\/10.1021\/ol006054v.","journal-title":"Org Lett"},{"key":"409_CR44","doi-asserted-by":"publisher","first-page":"14893","DOI":"10.1021\/ja027748x","volume":"124","author":"E Saxon","year":"2002","unstructured":"Saxon E, Luchansky SJ, Hang HC, Yu C, Lee SC, Bertozzi CR. Investigating cellular metabolism of synthetic azidosugars with the Staudinger ligation. J Am Chem Soc. 2002;124:14893\u2013902. https:\/\/doi.org\/10.1021\/ja027748x.","journal-title":"J Am Chem Soc"},{"key":"409_CR45","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.apradiso.2008.08.015","volume":"67","author":"PJH Scott","year":"2009","unstructured":"Scott PJH, Hockley BG, Kung HF, Manchanda R, Zhang W, Kilbourn MR. Studies into radiolytic decomposition of fluorine-18 labeled radiopharmaceuticals for positron emission tomography. Appl Radiat Isot. 2009;67:88\u201394. https:\/\/doi.org\/10.1016\/j.apradiso.2008.08.015.","journal-title":"Appl Radiat Isot"},{"key":"409_CR46","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1021\/ar200148z","volume":"44","author":"EM Sletten","year":"2011","unstructured":"Sletten EM, Bertozzi CR. From mechanism to mouse: a tale of two bioorthogonal reactions. Acc Chem Res. 2011;44:666\u201376. https:\/\/doi.org\/10.1021\/ar200148z.","journal-title":"Acc Chem Res"},{"key":"409_CR47","doi-asserted-by":"publisher","first-page":"8820","DOI":"10.1021\/ja060484k","volume":"128","author":"MB Soellner","year":"2006","unstructured":"Soellner MB, Nilsson BL, Raines RT. Reaction mechanism and kinetics of the traceless Staudinger ligation. J Am Chem Soc. 2006;128:8820\u20138. https:\/\/doi.org\/10.1021\/ja060484k.","journal-title":"J Am Chem Soc"},{"key":"409_CR48","doi-asserted-by":"publisher","first-page":"719","DOI":"10.3390\/pharmaceutics15030719","volume":"15","author":"N Soni","year":"2023","unstructured":"Soni N, Sarkar S, Bhise A, Ha YS, Park W, Yu A-R, et al. \u201cClick-to-clear\u201d: a strategy to minimize radioactivity from the blood pool utilizing staudinger ligation. Pharmaceutics. 2023;15:719. https:\/\/doi.org\/10.3390\/pharmaceutics15030719.","journal-title":"Pharmaceutics"},{"key":"409_CR49","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1002\/hlca.19190020163","volume":"2","author":"H Staudinger","year":"1919","unstructured":"Staudinger H, Meyer J. Ueber neue organische Phosphorverbindungen II. Phosphazine. Helv Chim Acta. 1919;2:619\u201335. https:\/\/doi.org\/10.1002\/hlca.19190020163.","journal-title":"Helv Chim Acta"},{"key":"409_CR50","doi-asserted-by":"publisher","first-page":"12117","DOI":"10.1002\/anie.201705346","volume":"56","author":"M Sundhoro","year":"2017","unstructured":"Sundhoro M, Jeon S, Park J, Ramstr\u00f6m O, Yan M. Perfluoroaryl azide Staudinger reaction: a fast and bioorthogonal reaction. Angew Chem Int Ed Engl. 2017;56:12117\u201321. https:\/\/doi.org\/10.1002\/anie.201705346.","journal-title":"Angew Chem Int Ed Engl"},{"key":"409_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-024-02898-3","volume":"22","author":"AR Sutherland","year":"2024","unstructured":"Sutherland AR, Parlekar B, Livingstone DW, Medina AX, Bernhard W, Garc\u00eda TH, et al. Antibody-targeted T cells and natural killer cells for cancer immunotherapy. J Nanobiotechnology. 2024;22:640. https:\/\/doi.org\/10.1186\/s12951-024-02898-3.","journal-title":"J Nanobiotechnology"},{"key":"409_CR52","doi-asserted-by":"publisher","first-page":"2072","DOI":"10.1021\/bc200298v","volume":"22","author":"DJ Vugts","year":"2011","unstructured":"Vugts DJ, Vervoort A, Stigter-van Walsum M, Visser GWM, Robillard MS, Versteegen RM, et al. Synthesis of phosphine and antibody-azide probes for in vivo staudinger ligation in a pretargeted imaging and therapy approach. Bioconjug Chem. 2011;22:2072\u201381. https:\/\/doi.org\/10.1021\/bc200298v.","journal-title":"Bioconjug Chem"},{"key":"409_CR53","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nchembio.2297","volume":"13","author":"H Wang","year":"2017","unstructured":"Wang H, Wang R, Cai K, He H, Liu Y, Yen J, et al. Selective in vivo metabolic cell-labeling-mediated cancer targeting. Nat Chem Biol. 2017;13:415\u201324. https:\/\/doi.org\/10.1038\/nchembio.2297.","journal-title":"Nat Chem Biol"},{"key":"409_CR54","doi-asserted-by":"publisher","first-page":"9482","DOI":"10.1002\/anie.201601123","volume":"55","author":"PR Wratil","year":"2016","unstructured":"Wratil PR, Horstkorte R, Reutter W. Metabolic glycoengineering with N-acyl side chain modified mannosamines. Angew Chem Int Ed Engl. 2016;55:9482\u2013512. https:\/\/doi.org\/10.1002\/anie.201601123.","journal-title":"Angew Chem Int Ed Engl"},{"key":"409_CR55","doi-asserted-by":"publisher","first-page":"7145","DOI":"10.3390\/molecules18067145","volume":"18","author":"X Zhang","year":"2013","unstructured":"Zhang X, Zhang Y. Applications of azide-based bioorthogonal click chemistry in glycobiology. Molecules. 2013;18:7145\u201359. https:\/\/doi.org\/10.3390\/molecules18067145.","journal-title":"Molecules"},{"key":"409_CR56","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3390\/ph18020277","volume":"18","author":"Q Zhang","year":"2025","unstructured":"Zhang Q, Hu Z, Zhao H, Du F, Lv C, Peng T, et al. Design, synthesis, and biological evaluation of a novel [18F]AlF-H3RESCA-FAPI radiotracer targeting fibroblast activation protein. Pharmaceuticals. 2025;18:277. https:\/\/doi.org\/10.3390\/ph18020277.","journal-title":"Pharmaceuticals"}],"container-title":["EJNMMI Radiopharmacy and Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41181-025-00409-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41181-025-00409-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41181-025-00409-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T12:35:31Z","timestamp":1765802131000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s41181-025-00409-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,9]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["409"],"URL":"https:\/\/doi.org\/10.1186\/s41181-025-00409-9","relation":{},"ISSN":["2365-421X"],"issn-type":[{"value":"2365-421X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,9]]},"assertion":[{"value":"15 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"79"}}