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Abstract：
Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells-Dawson polyoxometalate, α2-K10P2W17O61.20H2O (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol). The calculated X-ray attenuation linear slope for mono-WD POM was significantly higher compared to parent WD-POM, Keggin POM, and iohexol (5.97 ± 0.14 vs. 4.84 ± 0.05, 4.55 ± 0.16, and 4.30 ± 0.09, respectively). Acute oral (maximum-administered dose (MAD) = 960 mg/kg) and intravenous administration (1/10, 1/5, and 1/3 MAD) of mono-WD POM did not induce unexpected changes in rats\' general habits or mortality. Results of blood gas analysis, CO-oximetry status, and the levels of electrolytes, glucose, lactate, creatinine, and BUN demonstrated a dose-dependent tendency 14 days after intravenous administration of mono-WD POM. The most significant differences compared to the control were observed for 1/3 MAD, being approximately seventy times higher than the typically used dose (0.015 mmol W/kg) of tungsten-based contrast agents. The highest tungsten deposition was found in the kidney (1/3 MAD-0.67 ± 0.12; 1/5 MAD-0.59 ± 0.07; 1/10 MAD-0.54 ± 0.05), which corresponded to detected morphological irregularities, electrolyte imbalance, and increased BUN levels.
摘要：
最近，聚氧钨酸盐纳米团簇已成为有前途的计算机断层扫描（CT）造影剂。为了评估他们的临床潜力，在这项研究中，我们评估了体外CT成像特性，体内潜在的毒性作用，和单一元Wells-Dawson多金属氧酸盐的组织分布，α2-K10P2W17O61.20H2O(单-WDPOM)。与其他含钨纳米团簇（其母WD-POM和KegginPOM）和标准碘基造影剂（碘海醇）相比，Mono-WDPOM显示出更好的X射线衰减。与母体WD-POM相比，单WDPOM的X射线衰减线性斜率明显更高，KegginPOM,和碘海醇(5.97±0.14vs.分别为4.84±0.05、4.55±0.16和4.30±0.09）。单WDPOM的急性口服（最大给药剂量（MAD）=960mg/kg）和静脉内给药（1/10、1/5和1/3MAD）未引起大鼠一般习惯或死亡率的意外变化。血气分析结果,CO-血氧饱和度状态,和电解质的水平，葡萄糖，乳酸，肌酐,在静脉内施用单WDPOM后14天，BUN表现出剂量依赖性趋势。与对照组相比，观察到1/3MAD的最显著差异，比通常使用的钨基造影剂剂量(0.015mmolW/kg)高约70倍。在肾脏中发现了最高的钨沉积（1/3MAD-0.67±0.12；1/5MAD-0.59±0.07；1/10MAD-0.54±0.05），这对应于检测到的形态不规则性，电解质不平衡，增加BUN水平。
