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

ABSTRACT

BACKGROUND: 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. PURPOSE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.