{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T03:14:19Z","timestamp":1785467659536,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T00:00:00Z","timestamp":1573603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008393","name":"Teknologi og Produktion, Det Frie Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["0602-01911B (11-107077)"],"award-info":[{"award-number":["0602-01911B (11-107077)"]}],"id":[{"id":"10.13039\/100008393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004012","name":"Jane ja Aatos Erkon S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["to AR"],"award-info":[{"award-number":["to AR"]}],"id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: [68Ga]Ga-DOTA-Siglec-9 is a positron emission tomography (PET) radioligand for vascular adhesion protein 1 (VAP-1), a protein involved in leukocyte trafficking. The tracer facilitates the imaging of inflammation and infection. Here, we studied the pharmacokinetic modelling of [68Ga]Ga-DOTA-Siglec-9 in osteomyelitis and soft tissue infections in pigs. Methods: Eight pigs with osteomyelitis and soft tissue infections in the right hind limb were dynamically PET scanned for 60 min along with arterial blood sampling. The fraction of radioactivity in the blood accounted for by the parent tracer was evaluated with radio-high-performance liquid chromatography. One- and two-tissue compartment models were used for pharmacokinetic evaluation. Post-mortem soft tissue samples from one pig were analysed with anti-VAP-1 immunofluorescence. In each analysis, the animal\u2019s non-infected left hind limb was used as a control. Results: Tracer uptake was elevated in soft tissue infections but remained low in osteomyelitis. The kinetics of [68Ga]Ga-DOTA-Siglec-9 followed a reversible 2-tissue compartment model. The tracer metabolized quickly; however, taking this into account, produced more ambiguous results. Infected soft tissue samples showed endothelial cell surface expression of the Siglec-9 receptor VAP-1. Conclusion: The kinetics of [68Ga]Ga-DOTA-Siglec-9 uptake in porcine soft tissue infections are best described by the 2-tissue compartment model.<\/jats:p>","DOI":"10.3390\/molecules24224094","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T09:11:27Z","timestamp":1573636287000},"page":"4094","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Kinetic Modelling of [68Ga]Ga-DOTA-Siglec-9 in Porcine Osteomyelitis and Soft Tissue Infections"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6811-0172","authenticated-orcid":false,"given":"Lars","family":"J\u00f8dal","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Aalborg University Hospital, DK-9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-7977","authenticated-orcid":false,"given":"Anne","family":"Roivainen","sequence":"additional","affiliation":[{"name":"Turku PET Centre, Turku University Hospital, FI-20520 Turku, Finland"},{"name":"Turku PET Centre, University of Turku, FI-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1947-0219","authenticated-orcid":false,"given":"Vesa","family":"Oikonen","sequence":"additional","affiliation":[{"name":"Turku PET Centre, Turku University Hospital, FI-20520 Turku, Finland"},{"name":"Turku PET Centre, University of Turku, FI-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirpa","family":"Jalkanen","sequence":"additional","affiliation":[{"name":"MediCity Research Laboratory and Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2003-7292","authenticated-orcid":false,"given":"S\u00f8ren B.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Afzelius","sequence":"additional","affiliation":[{"name":"North Zealand Hospital, Hiller\u00f8d, Copenhagen University Hospital, DK-3400 Hiller\u00f8d, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aage K. O.","family":"Alstrup","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and PET, Aarhus University Hospital, DK-8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole L.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Copenhagen, DK-1870 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8575-3703","authenticated-orcid":false,"given":"Svend B.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Aalborg University Hospital, DK-9000 Aalborg, Denmark"},{"name":"Department of Chemistry and Biosciences, Aalborg University, DK-9100 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.2967\/jnumed.112.112524","article-title":"EANM\/SNMMI Guideline for 18F-FDG Use in Inflammation and Infection","volume":"54","author":"Jamar","year":"2013","journal-title":"J. Nucl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1007\/s00259-018-4052-x","article-title":"Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: An EANM procedural guideline","volume":"45","author":"Signore","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1053\/j.semnuclmed.2014.07.005","article-title":"Radionuclide imaging of osteomyelitis","volume":"45","author":"Palestro","year":"2015","journal-title":"Semin. Nucl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.nucmedbio.2015.05.002","article-title":"Quantification of the chromosomal radiation damage induced by labelling of leukocytes with [18F]FDG","volume":"42","author":"Chivato","year":"2015","journal-title":"Nucl. Med. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S1471-4906(01)01870-1","article-title":"VAP-1: An adhesin and an enzyme","volume":"22","author":"Salmi","year":"2001","journal-title":"Trends Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1161\/ATVBAHA.107.153130","article-title":"VAP-1 and CD73, endothelial cell surface enzymes in leukocyte extravasation","volume":"28","author":"Jalkanen","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s00259-011-1987-6","article-title":"Gallium-labelled peptides for imaging of inflammation","volume":"39","author":"Roivainen","year":"2012","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.1182\/blood-2010-09-311076","article-title":"Siglec-9 is a novel leukocyte ligand for vascular adhesion protein-1 and can be used in PET imaging of inflammation and cancer","volume":"118","author":"Aalto","year":"2011","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1089\/ars.2017.7418","article-title":"Vascular adhesion protein-1: A cell surface amine oxidase in translation","volume":"30","author":"Salmi","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13550-014-0045-3","article-title":"68Ga-DOTA-Siglec-9 PET\/CT imaging of peri-implant tissue responses and staphylococcal infections","volume":"4","author":"Ahtinen","year":"2014","journal-title":"EJNMMI Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1186\/s13075-017-1460-4","article-title":"Targeting of vascular adhesion protein-1 by positron emission tomography visualizes sites of inflammation in Borrelia burgdorferi-infected mice","volume":"19","author":"Siitonen","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_12","first-page":"18","article-title":"Feasibility of 68Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: A pilot study in a porcine model of acute respiratory distress syndrome","volume":"6","author":"Retamal","year":"2016","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7645070","DOI":"10.1155\/2017\/7645070","article-title":"Comparison of 68Ga-DOTA-Siglec-9 and 18F-fluorodeoxyribose-Siglec-9: Inflammation imaging and radiation dosimetry","volume":"2017","author":"Virtanen","year":"2017","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3109\/08941939.2012.718043","article-title":"A new technique for modeling of hematogenous osteomyelitis in pigs: Inoculation into femoral artery","volume":"26","author":"Johansen","year":"2013","journal-title":"J. Invest. Surg."},{"key":"ref_15","first-page":"257","article-title":"A non-traumatic Staphylococcus aureus osteomyelitis model in pigs","volume":"24","author":"Jensen","year":"2010","journal-title":"In Vivo"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jcpa.2012.01.018","article-title":"Pathology and biofilm formation in a porcine model of staphylococcal osteomyelitis","volume":"147","author":"Johansen","year":"2012","journal-title":"J. Comp. Pathol."},{"key":"ref_17","first-page":"169","article-title":"Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous staphylococcus aureus osteomyelitis model","volume":"5","author":"Nielsen","year":"2015","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13550-016-0251-2","article-title":"Blood perfusion in osteomyelitis studied with [15O] water PET in a juvenile porcine model","volume":"7","author":"Nielsen","year":"2017","journal-title":"EJNMMI Res."},{"key":"ref_19","first-page":"9256858","article-title":"Kinetic modelling of infection tracers [18F]FDG, [68Ga]Ga-citrate, [11C]methionine, and [11C]donepezil in a porcine osteomyelitis model","volume":"2017","author":"Jensen","year":"2017","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_20","first-page":"286","article-title":"Utility of 11C-methionine and 11C-donepezil for imaging of Staphylococcus aureus induced osteomyelitis in a juvenile porcine model: Comparison to autologous 111In-labelled leukocytes, 99mTc-DPD, and 18F-FDG","volume":"6","author":"Afzelius","year":"2016","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13550-019-0498-5","article-title":"An untapped potential for imaging of peripheral osteomyelitis in paediatrics using [18F] FDG PET\/CT\u2014The inference from a juvenile porcine model","volume":"9","author":"Afzelius","year":"2019","journal-title":"EJNMMI Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/jlcr.3525","article-title":"Exploring the radiosynthesis and in vitro characteristics of [68Ga]Ga-DOTA-Siglec-9","volume":"60","author":"Jensen","year":"2017","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_23","first-page":"1","article-title":"Refinement of a hematogenous localized osteomyelitis model in pigs","volume":"42","author":"Alstrup","year":"2016","journal-title":"Scand. J. Lab. Anim. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/SPC.0b013e3282f5272e","article-title":"Opioid-induced immunosuppression","volume":"2","author":"Sacerdote","year":"2008","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e01207-15","DOI":"10.1128\/genomeA.01207-15","article-title":"Whole-genome sequence of Staphylococcus aureus S54F9 isolated from a chronic disseminated porcine lung abscess and used in human infection models","volume":"3","author":"Jensen","year":"2015","journal-title":"Genome Announc."},{"key":"ref_26","first-page":"42","article-title":"Biodistribution of the radionuclides 18F-FDG, 11C-methionine, 11C-PK11195, and 68Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions","volume":"6","author":"Afzelius","year":"2016","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0002-9440(10)64558-0","article-title":"In vivo detection of vascular adhesion protein-1 in experimental inflammation","volume":"157","author":"Jaakkola","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_28","unstructured":"(2019, February 19). TPC List of Applications in TPCCLIB. Available online: http:\/\/www.turkupetcentre.net\/programs\/doc\/index.html."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1038\/sj.jcbfm.9600493","article-title":"Consensus nomenclature for in vivo imaging of reversibly binding radioligands","volume":"27","author":"Innis","year":"2007","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","article-title":"A new look at the statistical model identification","volume":"19","author":"Akaike","year":"1974","journal-title":"IEEE Trans. Autom. Control"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1177\/0049124104268644","article-title":"Multimodel inference: Understanding AIC and BIC in model selection","volume":"33","author":"Burnham","year":"2004","journal-title":"Sociol. Methods Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/jcbfm.1983.1","article-title":"Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data","volume":"3","author":"Patlak","year":"1983","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/jcbfm.1985.87","article-title":"Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations","volume":"5","author":"Patlak","year":"1985","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ejmp.2018.06.404","article-title":"[P083] Kinetic modelling of [68Ga]Ga-DOTA-Siglec-9 in a porcine infection model","volume":"52","author":"Roivainen","year":"2018","journal-title":"Phys. Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/22\/4094\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:34:00Z","timestamp":1760189640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/22\/4094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,13]]},"references-count":34,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["molecules24224094"],"URL":"https:\/\/doi.org\/10.3390\/molecules24224094","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,13]]}}}