Effect of stabilized iodized oil emulsion on experimentally induced hepatocellular carcinoma in rats.
OBJECTIVE
Previous studies have shown that the use of Lipiodol UltraFluid (LUF) emulsified with water leads to an increase in the tumoral uptake of iodine I 131-labeled LUF and reduced pulmonary uptake. Although emulsions containing LUF are currently used for chemoembolization of hepatocellular carcinomas (HCCs), this approach is impossible with intraarterial radiation therapy (RT) because of the problems of radiation protection linked to instability of the emulsions. The aims of this study were to develop stabilized emulsions of radiolabeled LUF of different particle sizes and viscosities and to study its biodistribution in rats with HCC.


METHODS
An emulsifier made of polyethylene glycol and hydrogenated castor oil was used to stabilize emulsions containing water and technetium Tc 99m-labeled Super Six Sulfur LUF. The various emulsions were injected in the hepatic arteries of rats with HCC. Twenty-four hours after injection, the rats were killed and the liver, tumor, and lungs were removed to perform ex-vivo gamma-counting to quantify tumoral, hepatic, and pulmonary uptake.


RESULTS
Emulsions of oil in water and water in oil of different viscosities (0.68-1.06 Pa.S) and particle size distributions (21-45 mum) were prepared and kept stable for more than 24 hours. Whatever the type of emulsion, the observed effect on tumoral uptake was the opposite of that expected. Indeed, a decrease in tumoral activity was observed (P < .05 in three of five cases) and a tendency toward increased pulmonary activity was observed (P < .05 in two of five cases) rather than any significant decrease.


CONCLUSIONS
This study made it possible to develop emulsions of radiolabeled iodized oil that remain stable for more than 24 hours. However, studies of biodistribution in rats with HCC failed to demonstrate any improvement in tumoral targeting, but rather showed a decrease in tumoral uptake that renders this approach impractical for intraarterial radiolabeled iodized oil RT as well as for intraarterial iodized oil chemoembolization. These results may possibly be explained by the use of an emulsifier containing lipophilic and hydrophilic components that modify the properties of LUF.
Garin
Etienne
E
UPRES EA 3890/Nuclear Medicine Service, Centre Eugène Marquis, rue de la Bataille Flanders Dunkerque, CS 44229, 35042 Rennes Cedex, France. etienne.garin@univ-rennes1.fr
Denizot
Benoit
B
Roux
Jérôme
J
Noiret
Nicolas
N
Lepareur
Nicolas
N
Moreau
Myriam
M
Mesba
Abiba
A
Laurent
Jean-François
JF
Herry
Jean-Yves
JY
Bourguet
Patrick
P
Benoit
Jean-Pierre
JP
Lejeune
Jean-Jacques
JJ
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D003287:Contrast Media / Q000378:metabolism*; D004655:Emulsions; D005260:Female; D007459:Iodized Oil / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014783:Viscosity
D003287:Contrast Media; D004655:Emulsions; D007459:Iodized Oil