Targeted alpha therapies using ²¹¹At: A Geant4 simulation of dose and DNA damage

Introduction: Targeted alpha therapies show great potential for cancer treatment due to their high linear energy transfer (LET) and low range. ²¹¹At is currently employed in clinical trials. Targeted alpha therapies (TAT) are effective as an adjuvant treatment for cancer or to treat micrometastases and diffuse cancers. A deeper understanding of the induced initial damage is crucial to enhance treatment planning.

Methods: This study shows Geant4(-DNA)-based simulations to calculate absorbed dose profiles and DNA damaging potential in intravenously administered TAT with ²¹¹At. It assumes radionuclide decay on the blood vessel wall, and calculates the DNA damage in the surrounding tissue.

Results: The calculated dosimetric quantities show that the effect of such treatment is mainly due to the emitted alpha particles, and is localised in a region of up to 80μm from the blood vessel. The RBE of the treatment is in the range 2.5-4, and is calculated as a function of the number of double-strand breaks.

Conclusions: Targeted therapies with ²¹¹At are effective within the range of the emitted alpha particles. With its capacity to induce complex DNA damage in such a short range, it is very promising for localised treatment of small tumour cells or micrometastases.