Effect of microdistribution of alpha and beta-emitters in targeted radionuclide therapies on delivered absorbed dose in a GATE model of bone marrow.

Acute hematologic toxicity is a frequent adverse effect of beta-emitter targeted radionuclide therapies (TRTs). Alpha emitters have the potential of delivering high linear energy transfer (LET) radiation to the tumor attributed to its shorter range. Antibody-based TRTs have increased blood-pool half-lives, and therefore increased marrow toxicity, which is a particular concern with alpha emitters. Accurate 3D absorbed dose calculations focusing on the interface region of blood vessels and bone can elucidate energy deposition patterns. Firstly, a cylindrical geometry model with a central blood vessel embedded in the trabecular tissue was modeled. Monte Carlo simulations in GATE were performed considering beta (177Lu, 90Y) and alpha emitters (211At, 225Ac) as sources restricted to the blood pool. Subsequently, the radioactive sources were added in the trabecular bone compartment in order to model bone marrow metastases infiltration (BMMI). Radial profiles, dose-volume histograms and voxel relative differences were used to evaluate the absorbed dose results. We demonstrated that alpha emitters have a higher localized energy deposition compared to beta emitters. In the cylindrical geometry model, when the sources are confined to the blood pool, the dose to the trabecular bone is greater for beta emitting radionuclides, as alpha emitters deposit the majority of their energy within 70 μm of the vessel wall. In the BMMI model, alpha emitters have a lower dose to untargeted trabecular bone. Our results suggest that when alpha emitters are restricted to the blood pool, as when labeled to antibodies, hematologic toxicities may be lower than expected due to differences in the microdistribution of delivered absorbed dose.