Humphreys J A, Priest N D, Ishikawa Y
Biomedical Research, AEA Technology, Oxon, UK.
Health Phys. 1998 Apr;74(4):442-7. doi: 10.1097/00004032-199804000-00004.
Thorotrast, a 25% colloidal suspension of 232ThO2, was formerly used as a radiographic contrast medium. Although epidemiological studies have shown that alpha particles emitted from 232Th and its decay products incorporated in the bone marrow cause leukemia, the use of these data for alpha particle induced leukemogenesis risk estimation has been criticized mainly for inhomogeneity of Thorotrast distribution. Four monkeys were injected with Thorotrast to investigate the degree of inhomogeneity in the thorium content of different bone marrow sites and the cellular localization of Thorotrast. Two were injected via an artery and two via a vein and sacrificed either at 1 wk or 3 to 4 y after injection. Microscopic, solid state autoradiography and back scatter electron imaging methods were applied to several bone sites to determine the degree of inhomogeneity. Quantification was performed using x-ray fluorescence for trabecular bone and bone marrow and neutron activation analysis for compact bones. At 1 wk Thorotrast was found to be distributed evenly in the red marrow; by 3 and 4 y conglomerates were seen which were restricted to macrophages. The monkey was found to be a good model for humans. The choice of injection route did not noticeably affect the Thorotrast distribution in bones of the skeletal system. Considering the even distribution of Thorotrast within the red bone marrow at early times after its injection, the inevitable diffusion of thorium progeny from the particles, the mobility of bone marrow macrophages, and the well established correction factor of self-absorption within conglomerates, these results suggest that data derived from Thorotrast patients are useful for risk estimation of alpha particle induced leukemia.
钍造影剂(Thorotrast),一种二氧化钍(232ThO2)的25%胶体悬浮液,曾被用作放射造影剂。尽管流行病学研究表明,232Th及其掺入骨髓的衰变产物发射的α粒子会导致白血病,但将这些数据用于α粒子诱发白血病风险评估主要受到钍造影剂分布不均匀性的批评。给四只猴子注射钍造影剂,以研究不同骨髓部位钍含量的不均匀程度以及钍造影剂的细胞定位。两只通过动脉注射,两只通过静脉注射,并在注射后1周或3至4年处死。对几个骨骼部位应用显微镜、固态放射自显影和背散射电子成像方法来确定不均匀程度。使用X射线荧光对小梁骨和骨髓进行定量分析,对密质骨进行中子活化分析。在1周时,发现钍造影剂均匀分布在红骨髓中;到3年和4年时,出现了局限于巨噬细胞的团块。发现猴子是人类的良好模型。注射途径的选择对钍造影剂在骨骼系统骨骼中的分布没有明显影响。考虑到钍造影剂在注射后早期在红骨髓内的均匀分布、钍子代从颗粒中不可避免的扩散、骨髓巨噬细胞的移动性以及团块内已确立的自吸收校正因子,这些结果表明,来自钍造影剂患者的数据可用于α粒子诱发白血病的风险评估。