EANM practical guidance on uncertainty analysis for molecular radiotherapy absorbed dose calculations

A framework is proposed for modelling the uncertainty in the measurement processes constituting the dosimetry chain that are involved in internal absorbed dose calculations. The starting point is the basic model for absorbed dose in a site of interest as the product of the cumulated activity and a dose factor. In turn, the cumulated activity is given by the area under a time–activity curve derived from a time sequence of activity values. Each activity value is obtained in terms of a count rate, a calibration factor and a recovery coefficient (a correction for partial volume effects). The method to determine the recovery coefficient and the dose factor, both of which are dependent on the size of the volume of interest (VOI), are described. Consideration is given to propagating estimates of the quantities concerned and their associated uncertainties through the dosimetry chain to obtain an estimate of mean absorbed dose in the VOI and its associated uncertainty. This approach is demonstrated in a clinical example

Potential of Optimal Preloading in Anti-CD20 Antibody Radioimmunotherapy: An Investigation Based on Pharmacokinetic Modeling

Recently, it has been suggested that the concept of preloading is limited by using a standard amount of unlabeled antibody. To identify the potential of optimal preloading, a pharmacokinetic model that describes the biodistribution of anti-CD20 antibody was developed. Simulations were conducted for different tumor burdens, spleen sizes, and tumor permeabilities. The optimal amount of unlabeled antibody was determined for each scenario. These simulations show that the currently administered standard amount is not optimal. A preload of 150 mg or lower would result in equal or higher tumor uptake in all cases. For tumors with high permeability, the uptake of labeled antibody could be increased by a factor of 8.5 using the considerably reduced optimal preload. The most sensitive parameter for the choice of the optimal amount of unlabeled antibody is the tumor uptake index. The results indicate that a personalized approach for radioimmunotherapy (RIT) with anti-CD20 antibody is required to account for the interpatient variability. The optimal amount of unlabeled antibody, which has to be determined by using a pharmacokinetic model, could substantially improve tumor uptake and thus RIT with anti-CD20 antibody