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在小鼠模型中对90Y、188Re、166Ho、149Pm、64Cu和177Lu放射性核素的β吸收分数评估。

Evaluation of beta-absorbed fractions in a mouse model for 90Y, 188Re, 166Ho, 149Pm, 64Cu, and 177Lu radionuclides.

作者信息

Miller William H, Hartmann-Siantar Christine, Fisher Darrell, Descalle Marie-Anne, Daly Tom, Lehmann Joerg, Lewis Michael R, Hoffman Timothy, Smith Jeff, Situ Peter D, Volkert Wynn A

机构信息

Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211, USA.

出版信息

Cancer Biother Radiopharm. 2005 Aug;20(4):436-49. doi: 10.1089/cbr.2005.20.436.

Abstract

Several short-lived, high-energy beta emitters are being proposed as the radionuclide components for molecular- targeted potential cancer therapeutic agents. The laboratory mice used to determine the efficacy of these new agents have organs that are relatively small compared to the ranges of these high-energy particles. The dosimetry model developed by Hui et al. was extended to provide realistic beta-dose estimates for organs in mice that received therapeutic radiopharmaceuticals containing (90)Y, (188)Re, (166)Ho, (149)Pm, (64)Cu, and (177)Lu. Major organs in this model included the liver, spleen, kidneys, lungs, heart, stomach, small and large bowel, thyroid, pancreas, bone, marrow, carcass, and a 0.025-g tumor. The study as reported in this paper verifies their results for (90)Y and extends them by using their organ geometry factors combined with newly calculated organ self-absorbed fractions from PEREGRINE and MCNP. PEREGRINE and MCNP agree to within 8% for the worst-case organ with average differences (averaged over all organs) decreasing from 5% for (90)Y to 1% for (177)Lu. When used with typical biodistribution data, the three different models predict doses that are in agreement to within 5% for the worst-case organ. The beta-absorbed fractions and cross-organ-deposited energy provided in this paper can be used by researchers to predict mouse-organ doses and should contribute to an improved understanding of the relationship between dose and radiation toxicity in mouse models where use of these isotopes is favorable.

摘要

几种短寿命、高能β发射体正被提议作为分子靶向潜在癌症治疗剂的放射性核素成分。用于确定这些新药剂疗效的实验室小鼠的器官与这些高能粒子的射程相比相对较小。Hui等人开发的剂量测定模型得到了扩展,以提供接受含(90)Y、(188)Re、(166)Ho、(149)Pm、(64)Cu和(177)Lu治疗性放射性药物的小鼠器官的实际β剂量估计值。该模型中的主要器官包括肝脏、脾脏、肾脏、肺、心脏、胃、小肠和大肠、甲状腺、胰腺、骨骼、骨髓、躯体以及一个0.025克的肿瘤。本文报道的研究验证了他们对(90)Y的结果,并通过将他们的器官几何因子与新计算的来自PEREGRINE和MCNP的器官自吸收分数相结合来扩展这些结果。对于最坏情况的器官,PEREGRINE和MCNP的结果在8%以内,平均差异(在所有器官上平均)从(90)Y的5%降至(177)Lu的1%。当与典型的生物分布数据一起使用时,三种不同的模型预测的剂量对于最坏情况的器官在5%以内是一致的。本文提供的β吸收分数和跨器官沉积能量可供研究人员用于预测小鼠器官剂量,并应有助于更好地理解在使用这些同位素有利的小鼠模型中剂量与辐射毒性之间的关系。

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