{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T10:44:33Z","timestamp":1781952273027,"version":"3.54.5"},"reference-count":89,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T00:00:00Z","timestamp":1671235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Studies of skeletal metabolism using measurements of bone metabolic flux (K<jats:sub>i<\/jats:sub>) obtained with [<jats:sup>18<\/jats:sup>F] sodium fluoride ([<jats:sup>18<\/jats:sup>F]NaF) positron emission tomography (PET) scans have been used in clinical research for the last 30 years. The technique has proven useful as an imaging biomarker in trials of novel drug treatments for osteoporosis and investigating other metabolic bone diseases, including chronic kidney disease mineral and bone disorder. It has also been shown to be valuable in metastatic bone disease in breast cancer patients and may have potential in other cancer types, such as prostate cancer, to assess early bone fracture risk. However, these studies have usually required a 60\u2010min dynamic PET scan and measurement of the arterial input function (AIF), making them difficult to translate into the clinic for diagnostic purposes. We have previously proposed a simplified method that estimates the K<jats:sub>i<\/jats:sub> value at an imaging site from a short (4\u2010min) static scan and venous blood samples. A key advantage of this method is that, by acquiring a series of static scans, values of K<jats:sub>i<\/jats:sub> can be quickly measured at multiple sites using a single injection of the tracer. To date, the widespread use of [<jats:sup>18<\/jats:sup>F]NaF PET has been limited by the need to measure the AIF required for the mathematical modeling of tracer kinetics to derive K<jats:sub>i<\/jats:sub> and other kinetic parameters. In this report, we review different methods of measuring the AIF, including direct arterial sampling, the use of a semi\u2010population input function (SP\u2010AIF), and image\u2010derived input function, the latter two requiring only two or three venous blood samples obtained between 30 and 60\u00a0min after injection. We provide an SP\u2010AIF model and a spreadsheet for calculating K<jats:sub>i<\/jats:sub> values using the static scan method that others can use to study bone metabolism in metabolic and metastatic bone diseases without requiring invasive arterial blood sampling. The method shortens scan times, simplifies procedures, and reduces the cost of multicenter trials without losing accuracy or precision.<\/jats:p>","DOI":"10.1002\/mp.16125","type":"journal-article","created":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T02:05:21Z","timestamp":1669428321000},"page":"2071-2088","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Input function and modeling for determining bone metabolic flux using [<sup>18<\/sup>F] sodium fluoride PET imaging: A step\u2010by\u2010step guide"],"prefix":"10.1002","volume":"50","author":[{"given":"Tanuj","family":"Puri","sequence":"first","affiliation":[{"name":"Faculty of Biology, Medicine and Health, School of Medical Sciences, Division of Cancer Sciences The University of Manchester, The Christie NHS Foundation Trust  Manchester UK"},{"name":"Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences King's College London, St.\u00a0Thomas\u2019 Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Frost","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research Clinical Trials &amp; Statistics Unit (ICR\u2010CTSU) The Institute of Cancer Research  Sutton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia E. B.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences King's College London, St.\u00a0Thomas\u2019 Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary J. R.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging, School of Biomedical Engineering and Imaging Sciences King's College London, St. Thomas\u2019 Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen M.","family":"Blake","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences King's College London, St.\u00a0Thomas\u2019 Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s8756\u20103282(03)00236\u20109"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.118.208710"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2021.110138"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.109.070052"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.114.146936"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","unstructured":"MuziM O'SullivanF PerkTG et\u00a0al.Whole\u2010Body [18F]\u2010Fluoride PET SUV imaging to monitor response to dasatinib Therapy in castration\u2010resistant prostate cancer bone metastases: secondary results from ACRIN 6687.Tomography.2021;7(2):139\u2010153. doi:10.3390\/tomography7020013","DOI":"10.3390\/tomography7020013"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000001186"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.050309"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169\u20106009(91)90086\u2010f"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.10.1846"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.070104"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.11.1932"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198\u2010012\u20102006\u2010x"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.07.081"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650111021"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365519709099408"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.040818"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20106649\u20109\u20103"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/tomography7040071"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02555045"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.106.037200"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198\u2010009\u20101005\u2010z"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.77.4.8408470"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115267"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010011\u20101966\u2010y"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/tomography7040053"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002\u2010021968"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.162"},{"issue":"10","key":"e_1_2_12_30_1","first-page":"1836","article-title":"SUV: standard uptake or silly useless value?","volume":"36","author":"Keyes JW","year":"1995","journal-title":"J Nucl Med"},{"issue":"5","key":"e_1_2_12_31_1","first-page":"633","article-title":"Evaluation of the skeletal kinetics of fluorine\u201018\u2010fluoride ion with PET","volume":"33","author":"Hawkins RA","year":"1992","journal-title":"J Nucl Med"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.111.093195"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1985.87"},{"issue":"9","key":"e_1_2_12_34_1","first-page":"1493","article-title":"Comparison of different quantitative approaches to 18F\u2010fluoride PET scans","volume":"45","author":"Brenner W","year":"2004","journal-title":"J Nucl Med"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNM.0b013e3283512adb"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.113.135269"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.21037\/qims.2018.01.02"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.109.063263"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.05.031"},{"key":"e_1_2_12_40_1","unstructured":"Administration of Radioactive Substances Advisory Committee. Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources. Accessed June 1 2022https:\/\/www.gov.uk\/arsac"},{"issue":"3","key":"e_1_2_12_41_1","first-page":"5","volume":"32","year":"2002","journal-title":"Ann ICRP"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.725118"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.119.226498"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.119.230565"},{"key":"e_1_2_12_45_1","first-page":"1","volume-title":"The Biomedical Engineering Handbook, Fourth Edition, Biomedical Engineering Fundamentals, Section 1 Physiologic systems","author":"Schneck DJ","year":"2015"},{"key":"e_1_2_12_46_1","doi-asserted-by":"crossref","unstructured":"TavesDR.Electrophoretic mobility of serum fluoride.Nature.1968 Nov 9;220(5167):582\u2010583.https:\/\/doi.org\/10.1038\/220582a0","DOI":"10.1038\/220582a0"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1118\/1.3635220"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNM.0000000000001393"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1095\u20100397(00)00057\u20101"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNM.0b013e328194f1e3"},{"issue":"3","key":"e_1_2_12_51_1","first-page":"214","article-title":"Two\u2010dimensional vs three\u2010dimensional imaging in whole body oncologic PET\/CT: a Discovery\u2010STE phantom and patient study","volume":"51","author":"Bettinardi V","year":"2007","journal-title":"Q J Nucl Med Mol Imaging"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1109\/23.106715"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/b107410"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.12.2215"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002590050474"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410060502"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13550\u2010017\u20100324\u2010x"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNM.0b013e3283452918"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNM.0b013e328349716f"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNM.0b013e3283550275"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.305"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1862"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647\u2010199807000\u201000002"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13550\u2010021\u201000859\u20107"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12149\u2010015\u20101008\u20100"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223\u2010021\u201000874\u20109"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031\u20109155\/50\/15\/N03"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.4.763"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLU.0000000000002533"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010002\u20100797\u20102"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1998.13.8.1328"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNM.0000000000000047"},{"key":"e_1_2_12_73_1","doi-asserted-by":"crossref","unstructured":"FunckT LarcherK ToussaintPJ EvansAC ThielA. APPIAN:Automated pipeline for PET image analysis.Front Neuroinform.2018;12:64.https:\/\/doi.org\/10.3389\/fninf.2018.00064","DOI":"10.3389\/fninf.2018.00064"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12021\u2010018\u20109384\u2010y"},{"key":"e_1_2_12_75_1","doi-asserted-by":"crossref","unstructured":"TjerkaskiJ CervenkaS FardeL MathesonGJ.Kinfitr\u2010an open\u2010source tool for reproducible PET modelling: validation and evaluation of test\u2010retest reliability.EJNMMI Res.2020;10(1):77.https:\/\/doi.org\/10.1186\/s13550\u2010020\u201000664\u20108","DOI":"10.1186\/s13550-020-00664-8"},{"key":"e_1_2_12_76_1","unstructured":"AMIDE: Medical Imaging Data Examiner. Accessed June 1 2022http:\/\/amide.sourceforge.net\/"},{"key":"e_1_2_12_77_1","unstructured":"Carimas. Accessed June 1 2022https:\/\/turkupetcentre.fi\/carimas\/"},{"key":"e_1_2_12_78_1","doi-asserted-by":"crossref","unstructured":"COMKAT (Compartmental Model Kinetic Analysis Tool). Accessed June 1 2022.https:\/\/nmmitools.org\/2019\/01\/01\/comkat\/","DOI":"10.36548\/jismac.2019.1"},{"key":"e_1_2_12_79_1","unstructured":"KMtool: Kinetic Modeling Toolbox. Accessed June 1 2022.https:\/\/mscipio.github.io\/project\/kmtool\/"},{"key":"e_1_2_12_80_1","unstructured":"UCLA Tracer Kinetic Model Fitting (TKMF) Program. Accessed June 1 2022.https:\/\/nmmitools.org\/2019\/01\/01\/ucla_tkmf\/"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.891073"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018\u2010014\u20100147\u20107"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.2016.1151354"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A5348"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010019\u201004424\u20102"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1177\/1071100719882717"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2021.02.563"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2021.04.014"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.21037\/qims.2019.01.01"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223\u2010013\u20109778\u20107"}],"container-title":["Medical Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mp.16125","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mp.16125","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mp.16125","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T10:24:02Z","timestamp":1754043842000},"score":1,"resource":{"primary":{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/10.1002\/mp.16125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,17]]},"references-count":89,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/mp.16125"],"URL":"https:\/\/doi.org\/10.1002\/mp.16125","archive":["Portico"],"relation":{},"ISSN":["0094-2405","2473-4209"],"issn-type":[{"value":"0094-2405","type":"print"},{"value":"2473-4209","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,17]]},"assertion":[{"value":"2022-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}