Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with <sup>131</sup>I-CLR1404
Pharmacokinetic modeling of the radiopharmaceuticals used in molecular radiotherapy is an important step towards accurate radiation dosimetry of such therapies. In this paper, we present a pharmacokinetic model for CLR1404, a phospholipid ether analog that, labeled with <sup>124</sup>I/&...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/1999-4923/13/9/1497 |
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| author | Sara Neira Araceli Gago-Arias Isabel Gónzalez-Crespo Jacobo Guiu-Souto Juan Pardo-Montero |
| author_facet | Sara Neira Araceli Gago-Arias Isabel Gónzalez-Crespo Jacobo Guiu-Souto Juan Pardo-Montero |
| author_sort | Sara Neira |
| collection | DOAJ |
| description | Pharmacokinetic modeling of the radiopharmaceuticals used in molecular radiotherapy is an important step towards accurate radiation dosimetry of such therapies. In this paper, we present a pharmacokinetic model for CLR1404, a phospholipid ether analog that, labeled with <sup>124</sup>I/<sup>131</sup>I, has emerged as a promising theranostic agent. We follow a systematic approach for the model construction based on a decoupling process applied to previously published experimental data, and using the goodness-of-fit, Sobol’s sensitivity analysis, and the Akaike Information Criterion to construct the optimal form of the model, investigate potential simplifications, and study factor prioritization. This methodology was applied to previously published experimental human time-activity curves for 9 organs. The resulting model consists of 17 compartments involved in the CLR1404 metabolism. Activity dynamics in most tissues are well described by a blood contribution plus a two-compartment system, describing <i>fast</i> and <i>slow</i> uptakes. The model can fit both clinical and pre-clinical kinetic data of <sup>124</sup>I/<sup>131</sup>I. In addition, we have investigated how simple fits (exponential and biexponential) differ from the complete model. Such fits, despite providing a less accurate description of time-activity curves, may be a viable alternative when limited data is available in a practical case. |
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| format | Article |
| id | doaj.art-8d8f1443b248426e83f8c38f599e8cc7 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T07:18:27Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8d8f1443b248426e83f8c38f599e8cc72023-11-22T14:48:41ZengMDPI AGPharmaceutics1999-49232021-09-01139149710.3390/pharmaceutics13091497Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with <sup>131</sup>I-CLR1404Sara Neira0Araceli Gago-Arias1Isabel Gónzalez-Crespo2Jacobo Guiu-Souto3Juan Pardo-Montero4Group of Medical Physics and Biomathematics, Instituto de Investigación Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, SpainGroup of Medical Physics and Biomathematics, Instituto de Investigación Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, SpainGroup of Medical Physics and Biomathematics, Instituto de Investigación Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, SpainDepartment of Medical Physics, Centro Oncolóxico de Galicia, 15009 A Coruña, SpainGroup of Medical Physics and Biomathematics, Instituto de Investigación Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, SpainPharmacokinetic modeling of the radiopharmaceuticals used in molecular radiotherapy is an important step towards accurate radiation dosimetry of such therapies. In this paper, we present a pharmacokinetic model for CLR1404, a phospholipid ether analog that, labeled with <sup>124</sup>I/<sup>131</sup>I, has emerged as a promising theranostic agent. We follow a systematic approach for the model construction based on a decoupling process applied to previously published experimental data, and using the goodness-of-fit, Sobol’s sensitivity analysis, and the Akaike Information Criterion to construct the optimal form of the model, investigate potential simplifications, and study factor prioritization. This methodology was applied to previously published experimental human time-activity curves for 9 organs. The resulting model consists of 17 compartments involved in the CLR1404 metabolism. Activity dynamics in most tissues are well described by a blood contribution plus a two-compartment system, describing <i>fast</i> and <i>slow</i> uptakes. The model can fit both clinical and pre-clinical kinetic data of <sup>124</sup>I/<sup>131</sup>I. In addition, we have investigated how simple fits (exponential and biexponential) differ from the complete model. Such fits, despite providing a less accurate description of time-activity curves, may be a viable alternative when limited data is available in a practical case.https://www.mdpi.com/1999-4923/13/9/1497biokineticscompartmental modeliodinemolecular radiotherapyCLR1404 |
| spellingShingle | Sara Neira Araceli Gago-Arias Isabel Gónzalez-Crespo Jacobo Guiu-Souto Juan Pardo-Montero Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with <sup>131</sup>I-CLR1404 Pharmaceutics biokinetics compartmental model iodine molecular radiotherapy CLR1404 |
| title | Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with <sup>131</sup>I-CLR1404 |
| title_full | Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with <sup>131</sup>I-CLR1404 |
| title_fullStr | Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with <sup>131</sup>I-CLR1404 |
| title_full_unstemmed | Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with <sup>131</sup>I-CLR1404 |
| title_short | Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with <sup>131</sup>I-CLR1404 |
| title_sort | development of a compartmental pharmacokinetic model for molecular radiotherapy with sup 131 sup i clr1404 |
| topic | biokinetics compartmental model iodine molecular radiotherapy CLR1404 |
| url | https://www.mdpi.com/1999-4923/13/9/1497 |
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