Sensitivity of model-based calculations of red marrow dosimetry to changes in patient-specific parameters

We have investigated several of the key model parameters and assumptions involved in the calculation of red marrow absorbed dose in order to better understand the sensitivity of the predicted results to changes in these model features and the subsequent effect on correlations of the red marrow absorbed dose values with observed hematologic toxicity. Red marrow dose calculations based on measured blood activity concentrations (to determine red marrow cumulated activity) and measured total body cumulated activity have a mass-independent and mass-dependent term. Adjustments for patient mass should be made in these calculations when patients' lean body masses are more than 10% different from that in the assumed standard models. The blood-based red marrow dose methodology has the potential to provide a reasonable estimate of red marrow dose as long as there is no specific uptake in red marrow or bone due to the presence of free radionuclide, disease, or retention of activity due to metabolism by the reticuloendothelial system. If these additional sources of red marrow dose are present, the blood-based methodology will significantly underestimate red marrow dose. For radiometals, such as in (90)Y-labeled antibodies, bone or red marrow uptake of free yttrium or catabolized (90)Y products may have a significant impact on the calculated dose, assuming fairly low amounts of free (90)Y or marrow activity uptake (5-10%), even in the absence of disease in red marrow and/or bone. This is also true for (131)I-labeled antibodies, although to a lesser extent due to typically reduced activity retention in the bone marrow in the absence of disease and lack of bone uptake of free radionuclide. Radiation dose calculations for the red marrow must be made as carefully as possible, taking into account all possible sources of radiation dose, and considering all sources of uncertainties, in order to give the best possible correlations of radiation dose with observed toxicity.