title: Uncertainty and sensitivity analysis of biokinetic models for radiopharmaceuticals used in nuclear medicine.
abstract: Mathematical models for kinetics of radiopharmaceuticals in humans were developed and are used to estimate the radiation absorbed dose for patients in nuclear medicine by the International Commission on Radiological Protection and the Medical Internal Radiation Dose (MIRD) Committee. However, due to the fact that the residence times used were derived from different subjects, partially even with different ethnic backgrounds, a large variation in the model parameters propagates to a high uncertainty of the dose estimation. In this work, a method was developed for analysing the uncertainty and sensitivity of biokinetic models that are used to calculate the residence times. The biokinetic model of (18)F-FDG (FDG) developed by the MIRD Committee was analysed by this developed method. The sources of uncertainty of all model parameters were evaluated based on the experiments. The Latin hypercube sampling technique was used to sample the parameters for model input. Kinetic modelling of FDG in humans was performed. Sensitivity of model parameters was indicated by combining the model input and output, using regression and partial correlation analysis. The transfer rate parameter of plasma to other tissue fast is the parameter with the greatest influence on the residence time of plasma. Optimisation of biokinetic data acquisition in the clinical practice by exploitation of the sensitivity of model parameters obtained in this study is discussed.
authors.affiliation: Institute of Radiation Protection, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, D-85764 Neuherberg, Germany. wli@helmholtz-muenchen.de
authors.forename: W B
authors.initials: WB
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Hoeschen
mesh_terms: D003198:Computer Simulation; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18