Uncertainties in Internal Dose Calculations for Radiopharmaceuticals

Abstract

This paper presents a systematic analysis of the inherent uncertainty in internal dose calculations for radiopharmaceuticals. A generic equation for internal dose is presented, and the uncertainty in each of the individual terms is analyzed, with the relative uncertainty of all terms compared. The combined uncertainties in most radiopharmaceutical dose estimates will be typically at least a factor of 2 and may be considerably greater. In therapy applications, if patient-individualized absorbed doses are calculated, with attention being paid to accurate data gathering and analysis and measurement of individual organ volumes, many of the model-based uncertainties can be removed, and the total uncertainty in an individual dose estimate can be reduced to a value of perhaps 610%-20%. Radiation dose estimates for different diagnostic radiopharmaceuticals should be appreciated and considered, but small differences in dose estimates between radiopharmaceuticals should not be given too much importance when one is choosing radiopharmaceuticals for general clinical use. Diagnostic accuracy, ease of use, image quality, patient comfort, and other similar factors should predominate in the evaluation, with radiation dose being another issue considered while balancing risks and benefits appropriately.Key Words: radiobiology/dosimetry; radiopharmaceuticals; radiation safety; internal dose assessment; radiopharmaceuticals; uncertainty Radi ation dose estimates for radiopharmaceuticals are widely reported by different groups and individuals, using various modeling assumptions and computational techniques. The reported estimates are mean or median values for large populations of individuals and are sometimes reported with uncertainty estimates but usually as observed standard deviations (SD) and coefficients of variation for the group of subjects studied. In this paper, a systematic analysis of the inherent uncertainty in internal dose calculations for radiopharmaceuticals is presented. Each term of the dose equation is evaluated for its individual uncertainty, and an overall uncertainty is then evaluated (although not calculated analytically via classic error propagation, for reasons that will be explained).To evaluate the overall uncertainty in a radiation dose estimate, one must consider the uncertainty in each of the contributing terms. (Note that the generic word dose in this article may refer to a number of dose quantities, such as absorbed dose, equivalent dose, or effective dose. Most of the analysis in this paper regards the mean dose to whole organs-currently the most widely used quantity in internal dose analysis. Later, some brief discussion of the uncertainty in dose calculations at the tissue or cell level is provided, but a systematic analysis of uncertainty in these applications is not treated.) A generic equation for the average absorbed dose in a target region T (e.g., an organ or tissue with radiopharmaceutical uptake) may be shown as:where D T is mean absorbed dose (Gy or rad) to a target region of interest; Ã S...

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