{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:36:42Z","timestamp":1767854202274,"version":"3.49.0"},"reference-count":69,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["CRC\/TRR 67\/3"],"award-info":[{"award-number":["CRC\/TRR 67\/3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The inducible enzyme cyclooxygenase-2 (COX-2) and the subsequent synthesis of eicosanoids initiated by this enzyme are important molecular players in bone healing. In this pilot study, the suitability of a novel selective COX-2 inhibitor bearing a nitric oxide (NO)-releasing moiety was investigated as a modulator of healing a critical-size bone defect in rats. A 5 mm femoral defect was randomly filled with no material (negative control, NC), a mixture of collagen and autologous bone fragments (positive control, PC), or polycaprolactone-co-lactide (PCL)-scaffolds coated with two types of artificial extracellular matrix (aECM; collagen\/chondroitin sulfate (Col\/CS) or collagen\/polysulfated hyaluronic acid (Col\/sHA3)). Bone healing was monitored by a dual-tracer ([18F]FDG\/[18F]fluoride) approach using PET\/CT imaging in vivo. In addition, ex vivo \u00b5CT imaging as well as histological and immunohistochemical studies were performed 16 weeks post-surgery. A significant higher uptake of [18F]FDG, a surrogate marker for inflammatory infiltrate, but not of [18F]fluoride, representing bone mineralization, was observed in the implanted PCL-scaffolds coated with either Col\/CS or Col\/sHA3. Molecular targeting of COX-2 with NO-coxib had no significant effect on tracer uptake in any of the groups. Histological and immunohistochemical staining showed no evidence of a positive or negative influence of NO-coxib treatment on bone healing.<\/jats:p>","DOI":"10.3390\/ijms26062582","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T06:53:00Z","timestamp":1741848780000},"page":"2582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring a Nitric Oxide-Releasing Celecoxib Derivative as a Potential Modulator of Bone Healing: Insights from Ex Vivo and In Vivo Imaging Experiments"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0646-5808","authenticated-orcid":false,"given":"Christin","family":"Neuber","sequence":"first","affiliation":[{"name":"Department Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Niedenzu","sequence":"additional","affiliation":[{"name":"University Center for Orthopaedics, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at Technische Universit\u00e4t Dresden, Fetscherstrasse 74, 01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2135-5858","authenticated-orcid":false,"given":"Sabine","family":"Schulze","sequence":"additional","affiliation":[{"name":"University Center for Orthopaedics, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at Technische Universit\u00e4t Dresden, Fetscherstrasse 74, 01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4916-3794","authenticated-orcid":false,"given":"Markus","family":"Laube","sequence":"additional","affiliation":[{"name":"Department Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Hofheinz","sequence":"additional","affiliation":[{"name":"Department Positron Emission Tomography, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1141-6493","authenticated-orcid":false,"given":"Stefan","family":"Rammelt","sequence":"additional","affiliation":[{"name":"University Center for Orthopaedics, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at Technische Universit\u00e4t Dresden, Fetscherstrasse 74, 01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1610-1493","authenticated-orcid":false,"given":"Jens","family":"Pietzsch","sequence":"additional","affiliation":[{"name":"Department Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"},{"name":"Faculty of Chemistry and Food Chemistry, School of Science, Technische Universit\u00e4t Dresden, Bergstra\u00dfe 66, 01069 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/00003086-200002000-00003","article-title":"Bone graft materials. An overview of the basic science","volume":"371","author":"Bauer","year":"2000","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00590-017-2063-0","article-title":"Treatment of critical-sized bone defects: Clinical and tissue engineering perspectives","volume":"28","author":"Roddy","year":"2018","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S96","DOI":"10.1007\/s005860100282","article-title":"Osteoinduction, osteoconduction and osseointegration","volume":"10","author":"Albrektsson","year":"2001","journal-title":"Eur. Spine J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/jcp.24135","article-title":"Over-sulfated chondroitin sulfate derivatives induce osteogenic differentiation of hMSC independent of BMP-2 and TGF-beta1 signalling","volume":"228","author":"Buttner","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.msec.2016.09.071","article-title":"Collagen\/glycosaminoglycan coatings enhance new bone formation in a critical size bone defect\u2014A pilot study in rats","volume":"71","author":"Bernhardt","year":"2017","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3233\/CH-199208","article-title":"Biomaterials in repairing rat femoral defects: In vivo insights from small animal positron emission tomography\/computed tomography (PET\/CT) studies","volume":"73","author":"Neuber","year":"2019","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5561","DOI":"10.1016\/j.biomaterials.2006.06.034","article-title":"Coating of titanium implants with collagen, RGD peptide and chondroitin sulfate","volume":"27","author":"Rammelt","year":"2006","journal-title":"Biomaterials"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.4161\/biom.21563","article-title":"Surface modification of implants in long bone","volume":"2","author":"Rentsch","year":"2012","journal-title":"Biomatter"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/jbm.a.30572","article-title":"Collageneous matrix coatings on titanium implants modified with decorin and chondroitin sulfate: Characterization and influence on osteoblastic cells","volume":"77","author":"Bierbaum","year":"2006","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1007\/s10439-009-9731-0","article-title":"Embroidered and surface modified polycaprolactone-co-lactide scaffolds as bone substitute: In vitro characterization","volume":"37","author":"Rentsch","year":"2009","journal-title":"Ann. Biomed. Eng."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1002\/jcb.24814","article-title":"Artificial matrices with high-sulfated glycosaminoglycans and collagen are anti-inflammatory and pro-osteogenic for human mesenchymal stromal cells","volume":"115","author":"Hempel","year":"2014","journal-title":"J. Cell. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hempel, U., Preissler, C., Vogel, S., Moller, S., Hintze, V., Becher, J., Schnabelrauch, M., Rauner, M., Hofbauer, L.C., and Dieter, P. (2014). Artificial extracellular matrices with oversulfated glycosaminoglycan derivatives promote the differentiation of osteoblast-precursor cells and premature osteoblasts. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/938368"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/j.1600-051X.2009.01435.x","article-title":"Increased bone formation around coated implants","volume":"36","author":"Stadlinger","year":"2009","journal-title":"J. Clin. Periodontol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/jbm.a.32878","article-title":"Long-bone critical-size defects treated with tissue-engineered polycaprolactone-co-lactide scaffolds: A pilot study on rats","volume":"95","author":"Rentsch","year":"2010","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Schulze, S., Neuber, C., Moller, S., Pietzsch, J., Schaser, K.D., and Rammelt, S. (2023). Microdialysis Reveals Anti-Inflammatory Effects of Sulfated Glycosaminoglycanes in the Early Phase of Bone Healing. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032077"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3233\/CH-199102","article-title":"Adjuvant drug-assisted bone healing: Part I\u2014Modulation of inflammation","volume":"73","author":"Rothe","year":"2019","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_17","first-page":"1211","article-title":"Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair","volume":"110","author":"Zhang","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lin, H.N., and O\u2019Connor, J.P. (2014). Immunohistochemical localization of key arachidonic acid metabolism enzymes during fracture healing in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088423"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1002\/jor.23553","article-title":"Pro-inflammatory M1 macrophages promote Osteogenesis by mesenchymal stem cells via the COX-2-prostaglandin E2 pathway","volume":"35","author":"Lu","year":"2017","journal-title":"J. Orthop. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Anastasio, A.T., Paniagua, A., Diamond, C., Ferlauto, H.R., and Fernandez-Moure, J.S. (2020). Nanomaterial Nitric Oxide Delivery in Traumatic Orthopedic Regenerative Medicine. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.592008"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3233\/CH-199103","article-title":"Adjuvant drug-assisted bone healing: Part II\u2014Modulation of angiogenesis","volume":"73","author":"Rothe","year":"2019","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1152\/japplphysiol.00957.2013","article-title":"Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing","volume":"116","author":"Tomlinson","year":"2014","journal-title":"J. Appl. Physiol."},{"key":"ref_23","first-page":"45","article-title":"Molecular pathogenesis of fracture nonunion","volume":"14","author":"Ding","year":"2018","journal-title":"J. Orthop. Transl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/00003086-199908000-00030","article-title":"Nitric oxide mediated vasoreactivity during fracture repair","volume":"365","author":"Corbett","year":"1999","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.bone.2015.11.006","article-title":"Deficiency of inducible and endothelial nitric oxide synthase results in diminished bone formation and delayed union and nonunion development","volume":"83","author":"Meesters","year":"2016","journal-title":"Bone"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1302\/0301-620X.81B3.0810531","article-title":"Nitric oxide in fracture repair. Differential localisation, expression and activity of nitric oxide synthases","volume":"81","author":"Corbett","year":"1999","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Brandt, F., Ullrich, M., Seifert, V., Haase-Kohn, C., Richter, S., Kniess, T., Pietzsch, J., and Laube, M. (2022). Exploring Nitric Oxide (NO)-Releasing Celecoxib Derivatives as Modulators of Radioresponse in Pheochromocytoma Cells. Molecules, 27.","DOI":"10.3390\/molecules27196587"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1016\/j.bmcl.2015.05.059","article-title":"Novel (pyrazolyl)benzenesulfonamides with a nitric oxide-releasing moiety as selective cyclooxygenase-2 inhibitors","volume":"25","author":"Bechmann","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/BF00965836","article-title":"PET: A biological imaging technique","volume":"16","author":"Phelps","year":"1991","journal-title":"Neurochem. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00726-005-0215-8","article-title":"Principles of quantitative positron emission tomography","volume":"29","year":"2005","journal-title":"Amino Acids"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rogasch, J.M.M., Hofheinz, F., van Heek, L., Voltin, C.A., Boellaard, R., and Kobe, C. (2022). Influences on PET Quantification and Interpretation. Diagnostics, 12.","DOI":"10.3390\/diagnostics12020451"},{"key":"ref_32","first-page":"309","article-title":"On the metabolism of carcinoma cells","volume":"152","author":"Warburg","year":"1924","journal-title":"Biochem. Z."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1007\/s00259-021-05368-2","article-title":"18F-fluoro-2-deoxy-d-glucose (FDG) uptake. What are we looking at?","volume":"48","author":"Sambuceti","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"448","DOI":"10.7150\/thno.6592","article-title":"PET imaging of inflammation biomarkers","volume":"3","author":"Wu","year":"2013","journal-title":"Theranostics"},{"key":"ref_35","first-page":"633","article-title":"Evaluation of the Skeletal Kinetics of Fluorine-18-Fluoride Ion with PET","volume":"33","author":"Hawkins","year":"1992","journal-title":"J. Nucl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.actbio.2019.04.008","article-title":"18F-fluoride as a prognostic indicator of bone regeneration","volume":"90","author":"Mathavan","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Rentsch, C., Schneiders, W., Manthey, S., Rentsch, B., and Rammelt, S. (2014). Comprehensive histological evaluation of bone implants. Biomatter, 4.","DOI":"10.4161\/biom.27993"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"144855","DOI":"10.1016\/j.gene.2020.144855","article-title":"Alkaline phosphatase: Structure, expression and its function in bone mineralization","volume":"754","author":"Vimalraj","year":"2020","journal-title":"Gene"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrrheum.2014.164","article-title":"Fracture healing: Mechanisms and interventions","volume":"11","author":"Einhorn","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.phrs.2003.12.017","article-title":"Is there an inhibitory effect of COX-2 inhibitors on bone healing?","volume":"50","author":"Seidenberg","year":"2004","journal-title":"Pharmacol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1100\/tsw.2010.58","article-title":"Recent insights into the implication of nitric oxide in osteoblast differentiation and proliferation during bone development","volume":"10","author":"Saura","year":"2010","journal-title":"Sci. World J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1097\/00003086-200211000-00051","article-title":"Bone healing regulated by nitric oxide: An experimental study in rats","volume":"404","author":"Baldik","year":"2002","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.lfs.2018.07.011","article-title":"COX inhibitors and bone: A safer impact on osteoblasts by NO-releasing NSAIDs","volume":"208","author":"Aisa","year":"2018","journal-title":"Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Todd, E.A., Mirsky, N.A., Silva, B.L.G., Shinde, A.R., Arakelians, A.R.L., Nayak, V.V., Marcantonio, R.A.C., Gupta, N., Witek, L., and Coelho, P.G. (2024). Functional Scaffolds for Bone Tissue Regeneration: A Comprehensive Review of Materials, Methods, and Future Directions. J. Funct. Biomater., 15.","DOI":"10.3390\/jfb15100280"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110892","DOI":"10.1016\/j.eurpolymj.2021.110892","article-title":"A review of protein adsorption and bioactivity characteristics of poly \u03b5-caprolactone scaffolds in regenerative medicine","volume":"162","author":"Sheikh","year":"2022","journal-title":"Eur. Polym. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/0092-8674(91)90308-L","article-title":"Proteoglycans as modulators of growth factor activities","volume":"64","author":"Ruoslahti","year":"1991","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"13369","DOI":"10.1016\/S0021-9258(18)80001-1","article-title":"Proteoglycans in cell regulation","volume":"264","author":"Ruoslahti","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/jor.1100100604","article-title":"Identification of integrin cell-substratum adhesion receptors on cultured rat bone cells","volume":"10","author":"Brighton","year":"1992","journal-title":"J. Orthop. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1155\/S1110724304306017","article-title":"Adhesion to Vitronectin and Collagen I Promotes Osteogenic Differentiation of Human Mesenchymal Stem Cells","volume":"2004","author":"Salasznyk","year":"2004","journal-title":"BioMed Res. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8418","DOI":"10.1016\/j.biomaterials.2012.08.028","article-title":"The effect of the degree of sulfation of glycosaminoglycans on osteoclast function and signaling pathways","volume":"33","author":"Salbach","year":"2012","journal-title":"Biomaterials"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s00109-011-0843-2","article-title":"Regenerative potential of glycosaminoglycans for skin and bone","volume":"90","author":"Salbach","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s00259-005-0026-x","article-title":"Uptake of bone-seekers is solely associated with mineralisation! A study with Tc-99m-MDP, Sm-153-EDTMP and F-18-fluoride on osteoblasts","volume":"33","author":"Toegel","year":"2006","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"738","DOI":"10.3109\/17453670903487040","article-title":"PET scanning for evaluation of bone metabolism","volume":"80","author":"Sorensen","year":"2009","journal-title":"Acta Orthop."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Volaric, D., Zauhar, G., Chen, J., Jerbic Radetic, A.T., Omrcen, H., Raic, A., Pirovic, R., and Cvijanovic Peloza, O. (2024). The Effect of Low-Intensity Pulsed Ultrasound on Bone Regeneration and the Expression of Osterix and Cyclooxygenase-2 during Critical-Size Bone Defect Repair. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073882"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.3390\/ph3051668","article-title":"Effect of Non-Steroidal Anti-Inflammatory Drugs on Bone Healing","volume":"3","author":"Cottrell","year":"2010","journal-title":"Pharmaceuticals"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/2191-219X-1-11","article-title":"Imaging technologies for preclinical models of bone and joint disorders","volume":"1","author":"Tremoleda","year":"2011","journal-title":"EJNMMI Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1089\/ten.teb.2013.0635","article-title":"Preclinical imaging in bone tissue engineering","volume":"20","author":"Ventura","year":"2014","journal-title":"Tissue Eng. Part. B Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1002\/term.1862","article-title":"SPECT vs. PET monitoring of bone defect healing and biomaterial performance in vivo","volume":"10","author":"Ventura","year":"2016","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1007\/s11307-012-0592-9","article-title":"Evaluation of new bone formation in normal and osteoporotic rats with a 3-mm femur defect: Functional assessment with dynamic PET-CT (dPET-CT) using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) and 18F-fluoride","volume":"15","author":"Cheng","year":"2013","journal-title":"Mol. Imaging Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.injury.2013.11.023","article-title":"Preliminary evaluation of different biomaterials for defect healing in an experimental osteoporotic rat model with dynamic PET-CT (dPET-CT) using F-18-sodium fluoride (NaF)","volume":"45","author":"Cheng","year":"2014","journal-title":"Injury"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.12659\/MSM.891073","article-title":"Application of F-18-sodium fluoride (NaF) dynamic PET-CT (dPET-CT) for defect healing: A comparison of biomaterials in an experimental osteoporotic rat model","volume":"20","author":"Cheng","year":"2014","journal-title":"Med. Sci. Monit."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"23094990221076654","DOI":"10.1177\/23094990221076654","article-title":"Use of small animal PET-CT imaging for in vivo assessment of tendon-to-bone healing: A pilot study","volume":"30","author":"Schar","year":"2022","journal-title":"J. Orthop. Surg."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1515\/hsz-2021-0170","article-title":"Men who stare at bone: Multimodal monitoring of bone healing","volume":"402","author":"Schulze","year":"2021","journal-title":"Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1007\/s00264-013-2087-y","article-title":"Repair of segmental long-bone defects by stem cell concentrate augmented scaffolds: A clinical and positron emission tomography--computed tomography analysis","volume":"37","author":"Petri","year":"2013","journal-title":"Int. Orthop."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1007\/s11999-017-5250-8","article-title":"Can Spatiotemporal Fluoride (18F\u2212) Uptake be Used to Assess Bone Formation in the Tibia? A Longitudinal Study Using PET\/CT","volume":"475","author":"Lundblad","year":"2017","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1002\/term.2494","article-title":"Multimodal-3D imaging based on muMRI and muCT techniques bridges the gap with histology in visualization of the bone regeneration process","volume":"12","author":"Sinibaldi","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13550-016-0208-5","article-title":"Comparative evaluation of SUV, tumor-to-blood standard uptake ratio (SUR), and dual time point measurements for assessment of the metabolic uptake rate in FDG PET","volume":"6","author":"Hofheinz","year":"2016","journal-title":"EJNMMI Res."},{"key":"ref_68","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_69","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/jbmr.141","article-title":"Guidelines for assessment of bone microstructure in rodents using micro-computed tomography","volume":"25","author":"Bouxsein","year":"2010","journal-title":"J. Bone Miner. 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