Small-scale bone marrow dosimetry study for 225Ac

Abstract

Background

Targeted alpha therapy (TAT) with ²²⁵Ac-labelled radiopharmaceuticals is a growing therapeutic option for the treatment of various cancers. Due to the short range of alpha particles in tissue, the absorbed dose can be non-uniform on a microscopic scale. Therefore, understanding bone marrow toxicity in TAT requires small-scale dosimetry.

Method

We developed a voxelised trabecular bone model, based off µCT slices, with a voxel size of (37 × 37 × 37) µm³. A small-scale dosimetry study was performed to assess the marrow toxicity from uptake of unlabelled ²²⁵Ac in the trabecular bone. The Particle and Heavy Ion Transport Code System (PHITS) was used to simulate the decays and score the absorbed dose to each voxel from the alpha and beta emissions of the ²²⁵Ac decay chain.

Results

For the alpha decays on the trabecular surface, 43 % of the marrow voxels were irradiated. The maximum voxel dose for the marrow was 1.1 Gy, and the mean non-zero voxel dose was 0.2 Gy (σ = 0.2 Gy). The beta-emissions from the trabecular surface irradiated all the marrow voxels, with a mean voxel dose of 3.9 mGy (σ = 1.7 mGy).

Conclusion

Our model demonstrated a non-uniform absorbed dose profile to the red marrow due to alpha emissions on the trabecular bone surface. The alpha emissions irradiated less than half of the marrow voxels, while the beta emissions irradiated all marrow voxels. This could potentially suggest a lower marrow toxicity from alpha-emitters compared to beta-emitters when skeletal metastases are present.