Estimation of absorbed doses in computational mouse and human phantoms receiving ²²⁹ Th-derived free ²²⁵ Ac

<i>Objective</i>. Free ²²⁵Ac can result in off-target radiation exposure if present as a result of incomplete chelation or radiolytic degradation of ²²⁵Ac radiopharmaceuticals. This study assessed absorbed doses of ²²⁹Th-derived free ²²⁵Ac to major normal tissues and organs in mouse and human models.<i>Approach</i>. Biodistribution data were obtained<i>ex vivo</i>from SK-MEL-2 xenograft mice administered with [²²⁵Ac]AcCl₃derived from a²²⁹Th/²²⁵Ac generator. Uptake fractions of²²⁵Ac in selected tissues and organs were measured at 0.5, 2, 6, and 24 h postinjection (p.i.) via its gamma-emitting daughter,²²¹Fr, with a sample size of<i>n</i> = 4-5 per p.i. time point. Time-integrated activity coefficients (TIACs) were calculated by fitting the mouse uptake profiles and extrapolated to human models using relative mass scaling. Absorbed dose coefficients (ADCs) were then calculated according to the Medical Internal Radiation Dose formalism using S values of a mouse whole-body (MOBY) phantom and anthropomorphic adult male and female phantoms implemented in the OLINDA dosimetry software. Redistribution of²²¹Fr and²¹³Bi from the liver to kidneys was simulated by adjusting progeny-specific TIAC ratios in the mouse model.<i>Main results</i>. The liver received the highest absorbed dose, with ADCs of 2860 mGy kBq^-1in the MOBY phantom and 886-1080 mGy MBq^-1in the anthropomorphic phantoms. The skeletal and splenic ADCs were 84.3 and 20.3 mGy kBq^-1, respectively, in the MOBY phantom. ADCs in the other tissues and organs were low to moderate, with the brain receiving the least. Under simulated redistribution scenarios,²²¹Fr showed larger changes in mouse ADCs than²¹³Bi, increasing the renal ADCs by 7.5-30.5% and decreasing the hepatic ADCs by 8-31.8% for scale factors of 0.1-0.4.<i>Significance</i>. The liver, bone, and spleen were suggested as the primary dosimetric targets of²²⁹Th-derived free²²⁵Ac. The ADCs of free²²⁵Ac calculated in this work may serve as a preliminary reference for quality control of²²⁵Ac radiopharmaceuticals.