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平面γ闪烁显像——定量分析肺部干粉气雾剂沉积时需考虑的要点

Planar gamma scintigraphy--points to consider when quantifying pulmonary dry powder aerosol deposition.

作者信息

Bondesson Eva, Bengtsson Thomas, Borgström Lars, Nilsson Lars Erik, Norrgren Kristina, Trofast Eva, Wollmer Per

机构信息

AstraZeneca R&D Lund, SE-221 87, Lund, Sweden.

出版信息

Int J Pharm. 2003 Jun 4;258(1-2):227-40. doi: 10.1016/s0378-5173(03)00148-0.

Abstract

Methodological aspects of planar gamma scintigraphy used to quantify pulmonary aerosol deposition were investigated using an experimental dry powder formulation. Particles of micronized salbutamol sulphate were labelled with technetium-99m and admixed to an ordered mixture of unlabelled micronized salbutamol sulphate and larger carrier particles of lactose. The radioaerosol was administered to 24 healthy subjects, 12 in each of two consecutive, similarly designed studies. Pulmonary deposition was determined using two methods: repeated planar imaging, and pharmacokinetic assessments following charcoal co-administration to prevent gastrointestinal salbutamol absorption. After due consideration had been taken to ensure appropriate radiolabelling, image acquisition and processing procedures, a scintigraphic estimate of 26.2% (with 95% confidence interval of 24.2-28.4%) was obtained, which did not significantly differ from the pharmacokinetic estimate of 26.4% (24.4-28.7%). In summary, pre-study validation of the radiolabelling technique, quality control of radioaerosols produced during the study, correction for re-distribution of radiolabel from the lungs, selection of regions of interest, assessment of lung contours, correction for tissue attenuation of gamma rays and establishment of the actual recovery of radioactivity in the scintigraphic measurements could potentially affect the accuracy of the scintigraphic estimate of pulmonary deposition and, thus, should be carefully considered in the design or evaluation of any such study.

摘要

采用一种实验性干粉制剂,对用于定量肺部气溶胶沉积的平面γ闪烁扫描术的方法学方面进行了研究。将微粉化硫酸沙丁胺醇颗粒用99m锝标记,并与未标记的微粉化硫酸沙丁胺醇和较大的乳糖载体颗粒的有序混合物混合。将放射性气雾剂给予24名健康受试者,在两项连续的、设计相似的研究中,每项研究各有12名受试者。采用两种方法测定肺部沉积:重复平面成像,以及在同时给予活性炭以防止胃肠道吸收沙丁胺醇后进行药代动力学评估。在充分考虑以确保适当的放射性标记、图像采集和处理程序后,获得的闪烁扫描估计值为26.2%(95%置信区间为24.2 - 28.4%),与药代动力学估计值26.4%(24.4 - 28.7%)无显著差异。总之,放射性标记技术的研究前验证、研究期间产生的放射性气雾剂的质量控制、肺部放射性标记重新分布的校正、感兴趣区域的选择、肺轮廓的评估、γ射线组织衰减的校正以及闪烁扫描测量中放射性实际回收率的确定,都可能影响肺部沉积闪烁扫描估计的准确性,因此,在设计或评估任何此类研究时都应仔细考虑。

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