title: Stabilization Improves Theranostic Properties of Lipiodol®-Based Emulsion During Liver Trans-arterial Chemo-embolization in a VX2 Rabbit Model.
abstract: OBJECTIVE
  To demonstrate that stability is a crucial parameter for theranostic properties of Lipiodol®-based emulsions during liver trans-arterial chemo-embolization.
  
  
  METHODS
  We compared the theranostic properties of two emulsions made of Lipiodol®and doxorubicin in two successive animal experiments (One VX2 tumour implanted in the left liver lobe of 30 rabbits). Emulsion-1 reproduced one of the most common way of preparation (ratio of oil/water: 1/1), and emulsion-2 was designed to obtain a water-in-oil emulsion with enhanced stability (ratio of oil/water: 3/1, plus an emulsifier). The first animal experiment compared the tumour selectivity of the two emulsions: seven rabbits received left hepatic arterial infusion (HAI) of emulsion-1 and eight received HAI of emulsion-2. 3D-CBCT acquisitions were acquired after HAI of every 0.1 mL to measure the densities' ratios between the tumours and the left liver lobes. The second animal experiment compared the plasmatic and tumour doxorubicin concentrations after HAI of 1.5 mg of doxorubicin administered either alone (n = 3) or in emulsion-1 (n = 6) or in emulsion-2 (n = 6).
  
  
  RESULTS
  Emulsion-2 resulted in densities' ratios between the tumours and the left liver lobes that were significantly higher compared to emulsion-1 (up to 0.4 mL infused). Plasmatic doxorubicin concentrations (at 5 min) were significantly lower after HAI of emulsion-2 (19.0 μg/L) than emulsion-1 (275.3 μg/L, p < 0.01) and doxorubicin alone (412.0 μg/L, p < 0.001), and tumour doxorubicin concentration (day-1) was significantly higher after HAI of emulsion-2 (20,957 ng/g) than in emulsion-1 (8093 ng/g, p < 0.05) and doxorubicin alone (2221 ng/g, p < 0.01).
  
  
  CONCLUSIONS
  Stabilization of doxorubicin in a water-in-oil Lipiodol®-based emulsion results in better theranostic properties.
authors.affiliation: Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France. frederic.deschamps@gustaveroussy.fr.|UMR 8203, Université Paris-Saclay, 94805, Villejuif, France. frederic.deschamps@gustaveroussy.fr.
authors.forename: F
authors.initials: F
authors.lastname: Deschamps
authors.affiliation: Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France.
authors.forename: G
authors.initials: G
authors.lastname: Farouil
authors.affiliation: Guerbet, Guerbet France, 93600, Aulnays-sous-Bois, France.
authors.forename: W
authors.initials: W
authors.lastname: Gonzalez
authors.affiliation: Guerbet, Guerbet France, 93600, Aulnays-sous-Bois, France.
authors.forename: C
authors.initials: C
authors.lastname: Robic
authors.affiliation: UMR 8203, Université Paris-Saclay, 94805, Villejuif, France.|Univ Paris-Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.
authors.forename: A
authors.initials: A
authors.lastname: Paci
authors.affiliation: UMR 8203, Université Paris-Saclay, 94805, Villejuif, France.|Univ Paris-Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.
authors.forename: L M
authors.initials: LM
authors.lastname: Mir
authors.affiliation: Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France.|Univ Paris-Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.
authors.forename: L
authors.initials: L
authors.lastname: Tselikas
authors.affiliation: Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France.|Univ Paris-Sud, Université Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.
authors.forename: T
authors.initials: T
authors.lastname: de Baère
mesh_terms: D000818:Animals; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage*; D004655:Emulsions; D004998:Ethiodized Oil / Q000008:administration & dosage*; D008114:Liver Neoplasms, Experimental / Q000628:therapy*; D011817:Rabbits; D000068936:Theranostic Nanomedicine / Q000379:methods*
chemical_list: D004655:Emulsions; D004998:Ethiodized Oil; D004317:Doxorubicin
keywords: Chemo-embolization; Emulsion; Hepatocarcinoma; Hypervascular tumour; Lipiodol; Liver