Optimization of Hepatocarcinoma Uptake with Radiolabeled Lipiodol: Development of New Lipiodol Formulations with Increased Viscosity

Abstract

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.

Comparison of embolic effect between water‐in‐oil emulsion and microspheres in transarterial embolization for rat hepatocellular carcinoma model

“…32,33 Not only can W/O emulsion slowly release drugs, but also achieve a high embolic effect and increase tumor retention due to its high viscosity. [32][33][34][35] However, the emulsion produced by the current pumping technique using a three-way stopcock has limitations; the percentage of W/O is only approximately 70% and the droplet sizes and viscosity are unattainable. 36 To improve the properties of Lipiodol emulsion, a pumping emulsification device with a microporous glass membrane was developed.…”

“…In conventional TACE, it is known that the physicochemical characteristics of emulsion influence the therapeutic outcomes 32,33 . Not only can W/O emulsion slowly release drugs, but also achieve a high embolic effect and increase tumor retention due to its high viscosity 32–35 . However, the emulsion produced by the current pumping technique using a three‐way stopcock has limitations; the percentage of W/O is only approximately 70% and the droplet sizes and viscosity are unattainable 36 .…”

Efficacy of Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma with Glass Membrane Emulsification Device

“…W/O emulsion has been associated with a high embolic effect. It is known that the viscosity of W/O is higher than O/W [16,19] ; a high viscosity, which can increase its tumor retention [33]; a high drug carriage capacity; and a longer drug release time [34,35].…”

Recent technical advances in conventional transarterial chemoembolization for hepatocellular carcinoma in Japan

“…Water-in-oil (W/O) emulsion can achieve high embolization efficacy by slowly releasing the drug, while offering enhanced tumor retention due to the high viscosity of the emulsion. 19,[27][28][29][30][31] However, emulsions produced by the current pump method using three-way cocks have an important limitation, in that they can only achieve a W/O ratio of about 70%. 32 Emulsification devices were developed to improve the properties of ethiodized oil emulsions formed by the pumping method.…”