{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:00:36Z","timestamp":1788199236343,"version":"build-2803163510"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"PUTI Q1 Universitas Indonesia","award":["NKB-394\/UN2.RST\/HKP.05.00\/2024"],"award-info":[{"award-number":["NKB-394\/UN2.RST\/HKP.05.00\/2024"]}]},{"DOI":"10.13039\/100021828","name":"German Academic Exchange Service","doi-asserted-by":"publisher","award":["F\u00f6rderkennzeichen 57657089"],"award-info":[{"award-number":["F\u00f6rderkennzeichen 57657089"]}],"id":[{"id":"10.13039\/100021828","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008977","name":"Universit\u00e4t Ulm","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008977","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EJNMMI Phys"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>This study aimed to determine a mathematical model for accurately calculating time-integrated activities (TIAs) of target tissue in <jats:sup>131<\/jats:sup>I therapy for benign thyroid disease using the population-based model selection and non-linear mixed-effects (PBMS-NLME) method.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Biokinetic data of <jats:sup>131<\/jats:sup>I in target tissue were collected from seventy-three patients at 2, 6, 24, 48, and 96 (<jats:italic>N<\/jats:italic>\u2009=\u200953) or 120 (<jats:italic>N<\/jats:italic>\u2009=\u200920) h after oral capsule administration with 1\u00a0MBq <jats:sup>131<\/jats:sup>I. Based on the Akaike weight, the best sum-of-exponential function (SOEF) describing the biokinetic data was selected using PBMS-NLME modelling. Nine SOEF with three to six parameters (including the function from the European Association of Nuclear Medicine Standard Operational Procedure (EANM SOP)) were used. The fittings were repeated 1000 times with different starting values of the SOE parameters to find the optimal fit. Akaike weight was used to identify the performance of the best model from PBMS-NLME and the EANM SOP SOE function with individual fitting.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Based on the PBMS-NLME analysis, the SOEF <jats:inline-formula>\n                <jats:alternatives>\n                  <jats:tex-math>$$\\frac{{\\lambda_{1} }}{{\\lambda_{2} + \\lambda_{1} - \\lambda_{3} }}\\left( {e^{{ - \\left( {\\lambda_{3} + \\lambda_{phys} } \\right)t}} - e^{{ - \\left( {\\lambda_{1} + \\lambda_{2} + \\lambda_{phys} } \\right)t}} } \\right) + a_{1} e^{{ - \\left( {\\lambda_{1} + \\lambda_{2} + \\lambda_{phys} } \\right)t}}$$<\/jats:tex-math>\n                  <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                    <mml:mrow>\n                      <mml:mfrac>\n                        <mml:msub>\n                          <mml:mi>\u03bb<\/mml:mi>\n                          <mml:mn>1<\/mml:mn>\n                        <\/mml:msub>\n                        <mml:mrow>\n                          <mml:msub>\n                            <mml:mi>\u03bb<\/mml:mi>\n                            <mml:mn>2<\/mml:mn>\n                          <\/mml:msub>\n                          <mml:mo>+<\/mml:mo>\n                          <mml:msub>\n                            <mml:mi>\u03bb<\/mml:mi>\n                            <mml:mn>1<\/mml:mn>\n                          <\/mml:msub>\n                          <mml:mo>-<\/mml:mo>\n                          <mml:msub>\n                            <mml:mi>\u03bb<\/mml:mi>\n                            <mml:mn>3<\/mml:mn>\n                          <\/mml:msub>\n                        <\/mml:mrow>\n                      <\/mml:mfrac>\n                      <mml:mfenced>\n                        <mml:mrow>\n                          <mml:msup>\n                            <mml:mi>e<\/mml:mi>\n                            <mml:mrow>\n                              <mml:mo>-<\/mml:mo>\n                              <mml:mfenced>\n                                <mml:mrow>\n                                  <mml:msub>\n                                    <mml:mi>\u03bb<\/mml:mi>\n                                    <mml:mn>3<\/mml:mn>\n                                  <\/mml:msub>\n                                  <mml:mo>+<\/mml:mo>\n                                  <mml:msub>\n                                    <mml:mi>\u03bb<\/mml:mi>\n                                    <mml:mrow>\n                                      <mml:mi>phys<\/mml:mi>\n                                    <\/mml:mrow>\n                                  <\/mml:msub>\n                                <\/mml:mrow>\n                              <\/mml:mfenced>\n                              <mml:mi>t<\/mml:mi>\n                            <\/mml:mrow>\n                          <\/mml:msup>\n                          <mml:mo>-<\/mml:mo>\n                          <mml:msup>\n                            <mml:mi>e<\/mml:mi>\n                            <mml:mrow>\n                              <mml:mo>-<\/mml:mo>\n                              <mml:mfenced>\n                                <mml:mrow>\n                                  <mml:msub>\n                                    <mml:mi>\u03bb<\/mml:mi>\n                                    <mml:mn>1<\/mml:mn>\n                                  <\/mml:msub>\n                                  <mml:mo>+<\/mml:mo>\n                                  <mml:msub>\n                                    <mml:mi>\u03bb<\/mml:mi>\n                                    <mml:mn>2<\/mml:mn>\n                                  <\/mml:msub>\n                                  <mml:mo>+<\/mml:mo>\n                                  <mml:msub>\n                                    <mml:mi>\u03bb<\/mml:mi>\n                                    <mml:mrow>\n                                      <mml:mi>phys<\/mml:mi>\n                                    <\/mml:mrow>\n                                  <\/mml:msub>\n                                <\/mml:mrow>\n                              <\/mml:mfenced>\n                              <mml:mi>t<\/mml:mi>\n                            <\/mml:mrow>\n                          <\/mml:msup>\n                        <\/mml:mrow>\n                      <\/mml:mfenced>\n                      <mml:mo>+<\/mml:mo>\n                      <mml:msub>\n                        <mml:mi>a<\/mml:mi>\n                        <mml:mn>1<\/mml:mn>\n                      <\/mml:msub>\n                      <mml:msup>\n                        <mml:mi>e<\/mml:mi>\n                        <mml:mrow>\n                          <mml:mo>-<\/mml:mo>\n                          <mml:mfenced>\n                            <mml:mrow>\n                              <mml:msub>\n                                <mml:mi>\u03bb<\/mml:mi>\n                                <mml:mn>1<\/mml:mn>\n                              <\/mml:msub>\n                              <mml:mo>+<\/mml:mo>\n                              <mml:msub>\n                                <mml:mi>\u03bb<\/mml:mi>\n                                <mml:mn>2<\/mml:mn>\n                              <\/mml:msub>\n                              <mml:mo>+<\/mml:mo>\n                              <mml:msub>\n                                <mml:mi>\u03bb<\/mml:mi>\n                                <mml:mrow>\n                                  <mml:mi>phys<\/mml:mi>\n                                <\/mml:mrow>\n                              <\/mml:msub>\n                            <\/mml:mrow>\n                          <\/mml:mfenced>\n                          <mml:mi>t<\/mml:mi>\n                        <\/mml:mrow>\n                      <\/mml:msup>\n                    <\/mml:mrow>\n                  <\/mml:math>\n                <\/jats:alternatives>\n              <\/jats:inline-formula> was selected as the function most supported by the data. The Akaike weight of the best function was approximately 100%. The best SOEF from the PBMS-NLME approach shows a better performance in describing the biokinetic data of <jats:sup>131<\/jats:sup>I in the thyroid gland than the function from the EANM SOP with individual fitting, based on the Akaike weight.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The best mathematical model from the PBMS-NLME approach has one more free parameter than the EANM SOP function, which could lead to more accurate TIAs.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40658-025-00735-6","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T03:24:18Z","timestamp":1744082658000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Non-linear mixed-effects modelling and population-based model selection for 131I kinetics in benign thyroid disease"],"prefix":"10.1186","volume":"12","author":[{"given":"Deni","family":"Hardiansyah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ade","family":"Riana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heribert","family":"H\u00e4nscheid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambros J.","family":"Beer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lassmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-1576","authenticated-orcid":false,"given":"Gerhard","family":"Glatting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"issue":"7","key":"735_CR1","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1007\/s00259-013-2387-x","volume":"40","author":"H H\u00e4nscheid","year":"2013","unstructured":"H\u00e4nscheid H, et al. EANM dosimetry committee series on standard operational procedures for pre-therapeutic dosimetry II. Dosimetry prior to radioiodine therapy of benign thyroid diseases. Eur J Nucl Med Mol Imaging. 2013;40(7):1126\u201334.","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"4","key":"735_CR2","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.zemedi.2013.03.005","volume":"23","author":"G Glatting","year":"2013","unstructured":"Glatting G, Bardi\u00e8s M, Lassmann M. Treatment planning in molecular radiotherapy. Z Med Phys. 2013;23(4):262\u20139.","journal-title":"Z Med Phys"},{"issue":"10","key":"735_CR3","doi-asserted-by":"publisher","DOI":"10.1118\/1.4820367","volume":"40","author":"P Kletting","year":"2013","unstructured":"Kletting P, et al. Molecular radiotherapy: the NUKFIT software for calculating the time-integrated activity coefficient. Med Phys. 2013;40(10): 102504.","journal-title":"Med Phys"},{"issue":"4","key":"735_CR4","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.zemedi.2011.01.006","volume":"21","author":"H H\u00e4nscheid","year":"2011","unstructured":"H\u00e4nscheid H, Lassmann M, Reiners C. Dosimetry prior to I-131-therapy of benign thyroid disease. Z Med Phys. 2011;21(4):250\u20137.","journal-title":"Z Med Phys"},{"issue":"8","key":"735_CR5","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1007\/s00228-018-2459-8","volume":"74","author":"V Topi\u0107 Vu\u010denovi\u0107","year":"2018","unstructured":"Topi\u0107 Vu\u010denovi\u0107 V, et al. Investigation of factors influencing radioiodine (131I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach. Eur J Clin Pharmacol. 2018;74(8):1037\u201345.","journal-title":"Eur J Clin Pharmacol"},{"issue":"1","key":"735_CR6","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s40658-021-00427-x","volume":"8","author":"D Hardiansyah","year":"2021","unstructured":"Hardiansyah D, et al. A population-based method to determine the time-integrated activity in molecular radiotherapy. EJNMMI Phys. 2021;8(1):82.","journal-title":"EJNMMI Phys"},{"key":"735_CR7","doi-asserted-by":"publisher","first-page":"103192","DOI":"10.1016\/j.ejmp.2023.103192","volume":"117","author":"OV Ivashchenko","year":"2024","unstructured":"Ivashchenko OV, O\u2019Doherty J, Hardiansyah D, Cremonesi M, Tran-Gia J, Hippel\u00e4inen E, Stokke C, Grassi E, Sandstr\u00f6m M, Glatting G. Time-activity data fitting in molecular radiotherapy: methodology and pitfalls. Physica Med. 2024;117:103192. https:\/\/doi.org\/10.1016\/j.ejmp.2023.103192.","journal-title":"Physica Med"},{"issue":"4","key":"735_CR8","doi-asserted-by":"publisher","first-page":"566","DOI":"10.2967\/jnumed.123.266268","volume":"65","author":"D Hardiansyah","year":"2024","unstructured":"Hardiansyah D, et al. Single-time-point renal dosimetry using nonlinear mixed-effects modeling and population-based model selection in [177Lu]Lu-PSMA-617 therapy. J Nucl Med. 2024;65(4):566\u201372.","journal-title":"J Nucl Med"},{"issue":"11","key":"735_CR9","doi-asserted-by":"publisher","first-page":"4285","DOI":"10.1118\/1.2794176","volume":"34","author":"G Glatting","year":"2007","unstructured":"Glatting G, et al. Choosing the optimal fit function: comparison of the Akaike information criterion and the F-test. Med Phys. 2007;34(11):4285\u201392.","journal-title":"Med Phys"},{"key":"735_CR10","unstructured":"Hardiansyah, D., et al., Population-Based Model Selection for an Accurate Estimation of Time-integrated Activity Using Non-Linear Mixed-Effects Modelling. Z Med Phys, epub 20 Feb 2023."},{"key":"735_CR11","volume-title":"Model selection and multimodel inference","author":"KP Burnham","year":"2002","unstructured":"Burnham KP, Anderson DR. Model selection and multimodel inference. New York: Springer-Verlag; 2002."},{"issue":"10","key":"735_CR12","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1118\/1.597421","volume":"22","author":"LE Williams","year":"1995","unstructured":"Williams LE, et al. On the correction for radioactive decay in pharmacokinetic modeling. Med Phys. 1995;22(10):1619\u201326.","journal-title":"Med Phys"},{"issue":"4","key":"735_CR13","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1118\/1.598561","volume":"26","author":"G Glatting","year":"1999","unstructured":"Glatting G, Reske SN. Treatment of radioactive decay in pharmacokinetic modeling: influence on parameter estimation in cardiac 13N-PET. Med Phys. 1999;26(4):616\u201321.","journal-title":"Med Phys"},{"key":"735_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.14","volume":"2","author":"DR Mould","year":"2013","unstructured":"Mould DR, Upton RN. Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods. CPT Pharmacometrics Syst Pharmacol. 2013;2: e38.","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"1","key":"735_CR15","doi-asserted-by":"publisher","first-page":"E60","DOI":"10.1208\/aapsj0901007","volume":"9","author":"RJ Bauer","year":"2007","unstructured":"Bauer RJ, Guzy S, Ng C. A survey of population analysis methods and software for complex pharmacokinetic and pharmacodynamic models with examples. AAPS J. 2007;9(1):E60-83.","journal-title":"AAPS J"},{"issue":"8","key":"735_CR16","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.2967\/jnumed.120.256255","volume":"62","author":"T Devasia","year":"2020","unstructured":"Devasia T, et al. A novel time-activity information sharing approach using nonlinear mixed models for patient-specific dosimetry with reduced imaging time points: application in SPECT\/CT imaging post 177Lu-DOTATATE. J Nucl Med. 2020;62(8):1118\u201325.","journal-title":"J Nucl Med"},{"issue":"1","key":"735_CR17","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.zemedi.2022.06.004","volume":"33","author":"D Hardiansyah","year":"2023","unstructured":"Hardiansyah D, et al. Single-time-point estimation of absorbed doses in PRRT using a non-linear mixed-effects model. Z Med Phys. 2023;33(1):70\u201381.","journal-title":"Z Med Phys"},{"key":"735_CR18","doi-asserted-by":"publisher","DOI":"10.1002\/9781118784860","volume-title":"Introduction to population pharmacokinetic \/ pharmacodynamic analysis with nonlinear mixed effects models","author":"JS Owen","year":"2014","unstructured":"Owen JS, Fiedler-Kelly J. Introduction to population pharmacokinetic \/ pharmacodynamic analysis with nonlinear mixed effects models. Wiley; 2014. https:\/\/doi.org\/10.1002\/9781118784860."},{"issue":"3","key":"735_CR19","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.zemedi.2009.05.003","volume":"19","author":"P Kletting","year":"2009","unstructured":"Kletting P, Glatting G. Model selection for time-activity curves: the corrected Akaike information criterion and the F-test. Z Med Phys. 2009;19(3):200\u20136.","journal-title":"Z Med Phys"},{"issue":"1","key":"735_CR20","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.zemedi.2022.10.001","volume":"33","author":"H H\u00e4nscheid","year":"2023","unstructured":"H\u00e4nscheid H, Lassmann M, Verburg FA. Determinants of target absorbed dose in radionuclide therapy. Z Med Phys. 2023;33(1):82\u201390.","journal-title":"Z Med Phys"},{"issue":"3","key":"735_CR21","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/S0031-6997(25)07323-5","volume":"4","author":"DS Riggs","year":"1952","unstructured":"Riggs DS. Quantitative aspects of iodine metabolism in man. Pharmacol Rev. 1952;4(3):284\u2013370.","journal-title":"Pharmacol Rev"},{"issue":"13","key":"735_CR22","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1007\/s00259-018-4136-7","volume":"45","author":"JI Gear","year":"2018","unstructured":"Gear JI, et al. EANM practical guidance on uncertainty analysis for molecular radiotherapy absorbed dose calculations. Eur J Nucl Med Mol Imag. 2018;45(13):2456\u201374.","journal-title":"Eur J Nucl Med Mol Imag"},{"key":"735_CR23","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-9485-1","volume-title":"Pharmacokinetic-pharmacodynamic modeling and simulation","author":"PL Bonate","year":"2011","unstructured":"Bonate PL. Pharmacokinetic-pharmacodynamic modeling and simulation. New York: Springer; 2011."}],"container-title":["EJNMMI Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40658-025-00735-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40658-025-00735-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40658-025-00735-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T16:53:33Z","timestamp":1744217613000},"score":1,"resource":{"primary":{"URL":"https:\/\/ejnmmiphys.springeropen.com\/articles\/10.1186\/s40658-025-00735-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,8]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["735"],"URL":"https:\/\/doi.org\/10.1186\/s40658-025-00735-6","relation":{},"ISSN":["2197-7364"],"issn-type":[{"value":"2197-7364","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,8]]},"assertion":[{"value":"22 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 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":"All authors read the manuscript and consented to its publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"37"}}