Centre Eugène Marquis, Nuclear Medicine Department, Rennes, France.
Cancer Biother Radiopharm. 2012 Mar;27(2):149-55. doi: 10.1089/cbr.2011.1072. Epub 2011 Dec 9.
The aim of this study was to develop new Lipiodol formulations with increased viscosities to augment Lipiodol embolic effect and optimize efficiency of radiolabeled Lipiodol in hepatocarcinoma treatments. New Lipiodol formulations consist of Lipiodol mixtures with different stearic acid concentrations (0.8%, 1.3%, and 1.8%). These formulations were fully characterized in vitro (viscosity, rheologic profiles) and labeled with 99mTc. Their viscosities at 20°C are 54, 60, and 67cP respectively, versus 45cP for Lipiodol ultra-fluide. Second, their biodistribution profiles were studied in vivo, at 24 and 72 hours, in hepatoma-bearing rats, and compared to control group (99mTc-Lipiodol). Biodistribution at 24 hours show a Gaussian tumor uptake profile with a maximum obtained with 1.3% stearic acid, and a tumor uptake superior to control group (+67%) (p<0.05). At 72 hours, optimal tumor uptake is reached with the 0.8% formulation, with 89% increase compared with control group (p<0.05). Moreover, we show a tendency to the decrease of pulmonary uptake for the new formulations at 24 hours and 72 hours. These results suggest a correlation between viscosity and Lipiodol tumor uptake. The new 0.8% stearic acid/Lipiodol formulation appears to be the optimized formulation for Lipiodol treatments of hepatocarcinoma, since it leads to a significant increase of tumor uptake at 72 hours and possibly to a decrease of undesirable pulmonary effects.
本研究旨在开发新型具有更高粘度的碘油制剂，以增强碘油栓塞效果，并优化放射性碘油在肝癌治疗中的效率。新型碘油制剂由不同硬脂酸浓度（0.8%、1.3%和 1.8%）的碘油混合物组成。这些制剂在体外（粘度、流变学特性）进行了充分的表征，并使用 99mTc 进行标记。它们在 20°C 时的粘度分别为 54、60 和 67cP，而超液态碘油的粘度为 45cP。其次，在荷肝癌大鼠体内，研究了它们在 24 和 72 小时时的体内分布特征，并与对照组（99mTc-碘油）进行了比较。24 小时的分布显示出肿瘤摄取的高斯分布特征，在 1.3%硬脂酸时获得最大摄取，并且比对照组（+67%）（p<0.05）更高。在 72 小时时，最佳的肿瘤摄取是通过 0.8%的制剂达到的，与对照组相比增加了 89%（p<0.05）。此外，我们还发现，新制剂在 24 小时和 72 小时时，肺摄取有减少的趋势。这些结果表明粘度与碘油肿瘤摄取之间存在相关性。新型 0.8%硬脂酸/碘油制剂似乎是治疗肝癌的优化碘油制剂，因为它可在 72 小时内显著增加肿瘤摄取，并且可能降低肺不良效应的风险。
