Murine-specific Internal Dosimetry for Preclinical Investigations of Imaging and Therapeutic Agents

There is a growing need to estimate the absorbed dose to small animals from preclinical investigations involving diagnostic and therapeutic radiopharmaceuticals. This paper introduces a Monte Carlo-based dosimetry platform called RAPID, which is capable of calculating murine-specific three-dimensional (3D) dose distributions. A comparison is performed between absorbed doses calculated with RAPID and absorbed doses calculated in a commonly used reference mouse phantom called MOBY. Four test mice containing different xenografts underwent serial PET/CT imaging using a novel diagnostic therapy (theranostic) agent NM404, which can be labeled with I for imaging or I for therapy. Using the PET/CT data, 3D dose distributions from I-NM404 were calculated in the mice using RAPID. Mean organ doses in these four test mice were compared to mean organ doses derived by using two previously published I S-values datasets in MOBY. In addition, mean tumor doses calculated in RAPID were compared to mean organ doses derived from unit density spheres. Large differences were identified between mean organ doses calculated in the test mice using RAPID and those derived in the MOBY phantom. Mean absorbed dose percent errors in organs ranged between 0.3% and 333%. Overall, mass scaling improved agreement between MOBY phantom calculations and RAPID, where percent errors were all less than 26%, with the exception of the lung in which percent errors reached values of 48%. Percent errors in mean tumor doses in the test mice and unit density spheres were less pronounced but still ranged between 8% and 23%. This work demonstrates the limitations of using pre-computed S-values in computational phantoms to predict organ doses in small animals from theranostic procedures. RAPID can generate accurate 3D dose distributions in small animals and in turn offer much greater insight on the ability of a given theranostic agent to image and treat diseases.