Modeling the effect of daughter migration on dosimetry estimates for unlabeled actinium-225

Actinium-225 (²²⁵Ac) is an alpha emitting radionuclide which has demonstrated promising results in Targeted Alpha Therapy (TAT). A concern with ²²⁵Ac is that the decay energy can break the bond to the targeting vehicle, resulting in the release of free alpha-emitting daughter radionuclides in the body.

The aim of this work is to develop a compartment model to describe the movement of unlabeled ²²⁵Ac in a human where the daughter isotopes of ²²⁵Ac have unique biokinetics.

The ICRP Occupational Intake of Radionuclides reports were used to construct a compartment model for the ²²⁵Ac decay chain where the daughter isotopes of ²²⁵Ac are assigned their own unique transfer coefficients (TCs) between compartments. Computer simulations were performed for unlabeled ²²⁵Ac uniformly placed in the plasma and only the dose from alpha particles was considered. Absorbed doses to normal organs were determined for the liver, kidneys, bone, soft tissue, active marrow, and blood. Simulations were performed for the case when: (1) the daughters have unique biokinetics and (2) the daughters decay at the site of ²²⁵Ac.

When the daughters have unique biokinetics, the organs that receive the highest absorbed dose are the liver (male: 1466.6 mGy/MBq, female: 1885.7 mGy/MBq), bone (male: 293.6 mGy/MBq, female: 403.6 mGy/MBq) and kidneys (male: 260.8 mGy/MBq, female: 294.0 mGy/MBq). These doses were compared to the case when the daughters of ²²⁵Ac decay at the site of ²²⁵Ac. There was a 13.5% increase in kidney dose, a 0.8% decrease in liver dose, and <0.1% decrease in bone dose calculations when the daughters have unique biokinetics compared to assuming the daughters decay at the site of ²²⁵Ac.

The kidneys received a large dose estimate (260-295 mGy/MBq) as well as a considerable change in dose of +13.5% when the daughters have unique biokinetics compared to assuming the daughters decay at the site of ²²⁵Ac. Therefore, to accurately determine the kidney dose from unlabeled ²²⁵Ac in a human, the biokinetics of the daughter isotopes should be considered.