Browsing by Author "Gonzalez-Crespo, Isabel"

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    Development of a Compartmental Pharmacokinetic Model for Molecular Radiotherapy with 131I-CLR1404
    (2021) Neira, Sara; Gago-Arias, Araceli; Gonzalez-Crespo, Isabel; Guiu-Souto, Jacobo; Pardo-Montero, Juan
    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 I-124/I-131, 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 fast and slow uptakes. The model can fit both clinical and pre-clinical kinetic data of I-124/I-131. 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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    Radiobiological Meta-Analysis of the Response of Prostate Cancer to Different Fractionations: Evaluation of the Linear-Quadratic Response at Large Doses and the Effect of Risk and ADT
    (2023) Pardo-Montero, Juan; Gonzalez-Crespo, Isabel; Gomez-Caamano, Antonio; Gago-Arias, Araceli
    Prostate cancer is currently treated with different radiotherapy fractionations, including extreme hypofractionation. Some studies suggest that the response to large radiation doses per fraction may depart from the response predicted by the widely used linear-quadratic (LQ) model. In this study, we analysed a large dataset of dose-response data to evaluate departures from the LQ behaviour at large doses. In general, the response of prostate cancer to large doses of radiotherapy is best described by the LQ model, even though we observed some discrepancies at large doses for intermediate-risk patients, which merit further investigation. In addition, we characterised the radiobiological response of prostate cancer according to risk (low, intermediate, or high) and the addition or not of ADT to treatment.