Internal dosimetry after incorporation of radionuclides requires standardized biokinetic and dosimetric models. The aim of the present work was to identify the parameters and the components of the models which contribute most to dosimetric uncertainty. For this a method was developed allowing for the calculation of the uncertainties of the absorbed dose coefficients. More specifically, the sampling-based regression method and the variance-based method were used to develop and apply a global method of sensitivity analysis. This method was then used to quantify the impact of various biokinetic and dosimetric parameters on the uncertainty of internal doses associated with the incorporation of seven common radiopharmaceuticals. It turned out that the correlation between biokinetic parameters and time-integrated activity or calculated absorbed dose is strongest when the source and target organ are identical, in accordance with the ICRP and the MIRD approach. According to the ICRP approach, the parameter Fs which describes the fractional distribution of any incorporated radioactivity to organ S, has the greatest correlation with the time-integrated activity in the corresponding source organ or with the calculated dose in the corresponding target organ. In contrast, the MIRD approach suggested several biokinetic parameters with similar correlation. The dosimetric parameters usually contribute more to uncertainty in the calculated dose coefficients than the biokinetic parameters, in both approaches. The results obtained are helpful for the revision of biokinetic models for radiopharmaceuticals, because the most important parameters in clinical applications can now be identified and investigated in future studies.
Keywords: Internal dosimetry; Nuclear medicine; Pharmacokinetic model; Uncertainty and sensitivity analysis; Voxel phantom.