Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody.
Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody.
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给予阳离子225标记的抗体后，苯uth-213的肾脏摄取及其对肾脏辐射剂量的贡献。
DOI：
10.1088/0031-9155/56/3/012
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发表时间：
2011-02-07
影响因子：
3.5
通讯作者：
Humm JL
中科院分区：
文献类型：
--
作者：
Schwartz J;Jaggi JS;O'Donoghue JA;Ruan S;McDevitt M;Larson SM;Scheinberg DA;Humm JL
使用225 Ac标记的抗体的临床治疗研究已经开始。主要关注的是可能由225 Ac衰变后产生的三个α-发射子代引起的肾毒性。本研究的目的是测定注射225 Ac-huM 195抗体后小鼠肾脏中225 Ac和非平衡子代的量，并检查剂量测定结果。在注射225 Ac-huM 195抗体后24、96和144小时处死小鼠组，并切除肾脏。一个肾脏用于通过高纯度锗（HPGe）检测器进行伽马射线光谱测量。第二个肾脏用于生成冷冻组织切片，通过数字放射自显影（DAR）进行检查。对每个肾脏标本进行两次测量：（1）切除后即刻和（2）任何非平衡过量213 Bi完全衰变的足够时间后。这些测量结果的比较使得能够估计到达肾脏的过量213 Bi的量（γ射线光谱法）及其子区域分布（DAR）。通过光谱学测定，整个肾脏的平均吸收剂量为0.77（SD 0.21）戈伊kBq−1，其中0.46（SD 0.16）戈伊kBq−1（即60%）是由于非平衡过量的213 Bi。通过DAR确定对肾皮质和髓质的相对贡献。来自非平衡过量213 Bi（0.31（SD 0.11）戈伊kBq−1）的皮质剂量估计值约占总量的46%。对于髓质，过量213 Bi（0.81（SD 0.28）戈伊kBq−1）的剂量贡献约为总剂量的80%。基于这些估计，对于人类患者，我们预测给予225 Ac-huM 195后肾脏吸收剂量为0.28戈伊MBq−1，其中非平衡过量213 Bi约占总量的60%。减少放射性子代肾蓄积的方法似乎是225 Ac放射免疫治疗成功所必需的。
Clinical therapeutic studies using 225Ac-labeled antibodies have begun. Of major concern is renal toxicity that may result from the three alpha-emitting progeny generated following the decay of 225Ac. The purpose of this study was to determine the amount of 225Ac and non-equilibrium progeny in the mouse kidney after the injection of 225Ac-huM195 antibody and examine the dosimetric consequences. Groups of mice were sacrificed at 24, 96 and 144 h after injection with 225Ac-huM195 antibody and kidneys excised. One kidney was used for gamma ray spectroscopic measurements by a high-purity germanium (HPGe) detector. The second kidney was used to generate frozen tissue sections which were examined by digital autoradiography (DAR). Two measurements were performed on each kidney specimen: (1) immediately post-resection and (2) after sufficient time for any non-equilibrium excess 213Bi to decay completely. Comparison of these measurements enabled estimation of the amount of excess 213Bi reaching the kidney (γ-ray spectroscopy) and its sub-regional distribution (DAR). The average absorbed dose to whole kidney, determined by spectroscopy, was 0.77 (SD 0.21) Gy kBq−1, of which 0.46 (SD 0.16) Gy kBq−1 (i.e. 60%) was due to non-equilibrium excess 213Bi. The relative contributions to renal cortex and medulla were determined by DAR. The estimated dose to the cortex from non-equilibrium excess 213Bi (0.31 (SD 0.11) Gy kBq−1) represented ~46% of the total. For the medulla the dose contribution from excess 213Bi (0.81 (SD 0.28) Gy kBq−1) was ~80% of the total. Based on these estimates, for human patients we project a kidney-absorbed dose of 0.28 Gy MBq−1 following administration of 225Ac-huM195 with non-equilibrium excess 213Bi responsible for approximately 60% of the total. Methods to reduce renal accumulation of radioactive progeny appear to be necessary for the success of 225Ac radioimmunotherapy.
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影响因子：
11.2
作者：
Song, Hong;Hobbs, Robert F.;Sgouros, George
通讯作者：
Sgouros, George
影响因子：
56.9
作者：
McDevitt, MR;Ma, DS;Scheinberg, DA
通讯作者：
Scheinberg, DA
影响因子：
20.3
作者：
Jurcic, JG;Larson, SM;Scheinberg, DA
通讯作者：
Scheinberg, DA
影响因子：
2.9
作者：
Miquel, G;Nekaa, T;Chahine, JME
通讯作者：
Chahine, JME
影响因子：
3.4
作者：
O'Donoghue, J
通讯作者：
O'Donoghue, J