Targeted alpha therapies using At: 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. At 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 At. 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 At 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.