title: 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.
authors.affiliation: Centre Eugène Marquis, Nuclear Medicine Department, Rennes, France. stephanie.becker@rouen.fnclcc.fr
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Becker
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lepareur
authors.forename: Virginie
authors.initials: V
authors.lastname: Cadeillan
authors.forename: Valérie
authors.initials: V
authors.lastname: Ardisson
authors.forename: Sahar
authors.initials: S
authors.lastname: Bayat
authors.forename: Nicolas
authors.initials: N
authors.lastname: Noiret
authors.forename: Etienne
authors.initials: E
authors.lastname: Garin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004998:Ethiodized Oil / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013229:Stearic Acids / Q000737:chemistry; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D014783:Viscosity
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D013229:Stearic Acids; C031183:stearic acid; D013667:Technetium; D004998:Ethiodized Oil