A trabecular model of bone marrow toxicity for ²²³Ra alpha-emitter radiopharmaceutical therapy

Objectives Ra-223, an α-particle emitting bone-seeking radionuclide has recently been used in clinical trials for osseous metasteses of prostate cancer. We investigated the relationship between absorbed fraction-based red marrow dosimetry and cell level-dosimetry using a model that accounts for the expected localization of this agent relative to marrow cavity architecture. We show that cell level-based dosimetry is essential to understanding potential marrow toxicity.

Methods The GEANT4 software package was used to create simple spheres representing marrow cavities. Ra-223 was positioned on the trabecular bone surface and simulated for decay, along with the daughter products. The interior of the sphere was divided into cell-size voxels and the energy was collected in each voxel and interpreted as dose cell histograms. The average dose values and absorbed fractions were also calculated in order to compare those results with previously published values.

Results The dose was predominantly deposited near the trabecular surface. The dose cell histograms results were used to plot the percentage of cells that received a potentially toxic dose (2 or 4 Gy) as a function of the average absorbed dose over the marrow cavity. The results show that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity resulted in only a small increase in the number of cells receiving a toxic dose, for a range of average marrow cavity absorbed doses from 1 Gy to 20 Gy.

Conclusions The results from the trabecular model differ markedly from a standard absorbed fraction method while presenting comparable average dose values. These suggest that increasing the amount of radioactivity will not substantially increase the risk of toxicity, a result unavailable to the absorbed fraction method of dose calculation