A dosimetric model for the heterogeneous delivery of radioactive nanoparticles In vivo: a feasibility study

Accurate and quantitative dosimetry for internal radiation therapy can be especially challenging, given the heterogeneity of patient anatomy, tumor anatomy, and source deposition. Internal radiotherapy sources such as nanoparticles and monoclonal antibodies require high resolution imaging to accurately model the heterogeneous distribution of these sources in the tumor. The resolution of nuclear imaging modalities is not high enough to measure the heterogeneity of intratumoral nanoparticle deposition or intratumoral regions, and mathematical models do not represent the actual heterogeneous dose or dose response. To help answer questions at the interface of tumor dosimetry and tumor biology, we have modeled the actual 3-dimensional dose distribution of heterogeneously delivered radioactive nanoparticles in a tumor after systemic injection.

24 h after systemic injection of dually fluorescent and radioactive nanoparticles into a tumor-bearing mouse, the tumor was cut into 342 adjacent sections and imaged to quantify the source distribution in each section. The images were stacked to generate a 3D model of source distribution, and a novel MATLAB code was employed to calculate the dose to cells on a middle section in the tumor using a low step size dose kernel.

The ability of this model to quantify the absorbed dose and dose response in different intratumoral regions allows one to investigate how source deposition in different tumor areas can affect dose and cytotoxicity, as well as how characteristics of the tumor microenvironment, such as hypoxia or high stromal areas, may affect the potency of a given dose.