Department of Physics, The University of Adelaide, Adelaide, South Australia, Australia.
Medical Physics & Radiation Safety, South Australia Medical Imaging, Adelaide, South Australia, Australia.
Med Phys. 2024 Jul;51(7):5032-5044. doi: 10.1002/mp.16917. Epub 2024 Jan 10.
Actinium-225 (Ac) is an alpha emitting radionuclide which has demonstrated promising results in Targeted Alpha Therapy (TAT). A concern with Ac 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 Ac in a human where the daughter isotopes of Ac have unique biokinetics.
The ICRP Occupational Intake of Radionuclides reports were used to construct a compartment model for the Ac decay chain where the daughter isotopes of Ac are assigned their own unique transfer coefficients (TCs) between compartments. Computer simulations were performed for unlabeled Ac 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 Ac.
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 Ac decay at the site of Ac. 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 Ac.
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 Ac. Therefore, to accurately determine the kidney dose from unlabeled Ac in a human, the biokinetics of the daughter isotopes should be considered.
锕-225（Ac）是一种发射阿尔法粒子的放射性核素，在靶向阿尔法治疗（TAT）中显示出了良好的效果。人们担心的是，Ac 的衰变能量可能会破坏与靶向载体的键，导致体内游离的发射阿尔法粒子的子放射性核素释放。
本工作旨在开发一个房室模型来描述未标记的 Ac 在人体内的运动，其中 Ac 的子同位素具有独特的生物动力学。
使用 ICRP 职业放射性核素摄入量报告构建 Ac 衰变链的房室模型，其中 Ac 的子同位素被分配各自独特的房室间转移系数（TCs）。对均匀分布在血浆中的未标记的 Ac 进行计算机模拟，仅考虑阿尔法粒子的剂量。确定肝脏、肾脏、骨骼、软组织、活跃骨髓和血液等正常器官的吸收剂量。对以下两种情况进行了模拟：（1）子同位素具有独特的生物动力学；（2）子同位素在 Ac 位置衰变。
当子同位素具有独特的生物动力学时，吸收剂量最高的器官是肝脏（男性：1466.6 mGy/MBq，女性：1885.7 mGy/MBq）、骨骼（男性：293.6 mGy/MBq，女性：403.6 mGy/MBq）和肾脏（男性：260.8 mGy/MBq，女性：294.0 mGy/MBq）。将这些剂量与 Ac 位置衰变的子同位素情况进行了比较。当子同位素具有独特的生物动力学时，与假设子同位素在 Ac 位置衰变相比，肾脏剂量增加了 13.5%，肝脏剂量减少了 0.8%，骨骼剂量减少了<0.1%。
与假设子同位素在 Ac 位置衰变相比，当子同位素具有独特的生物动力学时，肾脏的剂量估算值较大（260-295 mGy/MBq），剂量变化较大（+13.5%）。因此，为了准确确定人体内未标记的 Ac 的肾脏剂量，应考虑子同位素的生物动力学。
