Small scale modeling as a complement to personalized dosimetry

Full text of publication follows. Objectives: 3-dimensional dosimetry offers a number of specific advantages in terms of personalizing radiopharmaceutical therapy (RPT). Modern imaging modalities such as SPECT and PET, acquired at multiple time points after administration of pre-therapeutic activity, provide the data necessary for the 3-dimensional absorbed dose maps and subsequent personalized treatment planning. As such, any limitation of the imaging data, in particular the resolution, will inhibit the dosimetry. Geometric modeling can play an important role in complementing patient imaging and provide reliable personalized dosimetry. Methods: we illustrate this concept with several examples: (1) arterial wall dosimetry in 131-tositumomab therapy of non-Hodgkin's lymphoma, (2) salivary gland dosimetry in ¹³¹I therapy of thyroid cancer, and (3) renal toxicity from ²²⁵Ac therapy of metastatic breast cancer in a pre-clinical model. In each example, a geometrical model within the GEANT4 framework was created and Monte Carlo simulation was run to create S-values for the different compartments. Using imaging data acquired from the individual patient (or mouse), these S-values were then used to provide patient-specific dosimetric results. Results: absorbed doses were calculated in each example. For the arterial wall dosimetry, this led to the conclusion that for myelo-ablative regimes of RPT, the artery walls should be considered as potentially dose-limiting. For ¹³¹I salivary gland and renal alpha-particle modeling, this led to the result that localization of activity uptake is likely responsible for the discrepancies between calculated whole organ absorbed dose and observed toxicities. Conclusions: modeling is an important component in the progression of science, and is part of the interplay between theory and experiment. In the realm of personalized dosimetry, modeling can play a key role providing insight into absorbed dose to regions of interest smaller than the imaging resolution. (authors)