Quantitative whole-body kinetic analysis using longitudinal hybrid fluorescence molecular tomography
| Autor: | Zuo, Simin |
|---|---|
| Přispěvatelé: | Kiessling, Fabian, Boor, Peter |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Aachen : RWTH Aachen University 1 Online-Ressource : Illustrationen, Diagramme (2021). doi:10.18154/RWTH-2022-00036 = Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2021 |
| DOI: | 10.18154/RWTH-2022-00036 |
| Popis: | Dissertation, Rheinisch-Westf��lische Technische Hochschule Aachen, 2021; Aachen 1 Online-Ressource : Illustrationen, Diagramme (2022). = Dissertation, Rheinisch-Westf��lische Technische Hochschule Aachen, 2021 Longitudinal hybrid ��CT-FMT can provide three-dimensional biodistribution of fluorescent compounds and determine the pharmacokinetics profiles in major organs, enabling whole-body kinetic modeling. The real value and usefulness of the estimated kinetic parameters depend on the model's simplicity and the accuracy of pharmacokinetic data. In this thesis, a simplified whole-body pharmacokinetic modeling with mixing matrix correction was proposed. Accordingly, the kinetic parameters of the hepatobiliary and renal elimination routes and five major retention sites were investigated in simulations and in an in vivo study. Four NIR fluorescent compounds: indocyanine green (ICG), microbubbles (MB), nanogels (NG), and OsteoSense (OS), were evaluated in BALB/c nude mice using hybrid ��CT-FMT. In the simulations, the kinetic modeling with mixing matrix correction had low relative errors and strong linear relationships (slopes close to 1) between the estimated and simulated parameters. Furthermore, the modeling with more early sampling points at the pharmacokinetic process can significantly suppress noise in parameter estimation. For the in vivo study, it was observed that NG and ICG were significantly eliminated by the liver, while OS had significantly large renal elimination rates. MB and NG showed the highest hepatic retention rates, while OS had the highest bone retention. With mixing matrix correction, NG had higher hepatic retention rates, while OS had lower renal and hepatic retention rates than the uncorrected modeling. Additionally, using the corrected modeling, the bone retention rates of OS were significantly higher than the uncorrected modeling. In summary, the proposed kinetic modeling with mixing matrix correction proved to be robust and reliable in simulations. The corrected kinetic model enabled a more accurate estimation of physiologically meaningful parameters using pharmacokinetic data derived from hybrid ��CT-FMT. Published by Aachen |
| Databáze: | OpenAIRE |
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