Novel Injectable Fluorinated Contrast Agents with Enhanced Radiopacity

Abstract

Novel emulsions containing iodinated fluorinated radiopaque (IFR) molecules were prepared and evaluated as injectable contrast agents with prolonged intravascular persistence. Various stable IFR/egg yolk phospholipid emulsions were produced, heat-sterilized, and tested as to their radiopacity, shelf-stability and in vivo tolerance. No significant change in mean particle sizes was observed over a 3-month storage period at 40°C. Intravenous injection of an emulsion of a 0.39 g/kg bw dose of a typical IFR, C₆F₁₃CH=CIC₆H₁₃ (F6H6IE) in rabbits led to high contrast in the liver and spleen. The same radiopacity of the liver was achieved with 7 times less IFR than perfluorooctyl bromide. Histological examination after 24 h, and blood analysis after 24, 48 h and 7 days, demonstrated normal functioning of the liver, even when high concentrations of IFR were present. The neat IFR was tolerated i.p. in mice at a 45 g/kg bw dose. Emulsified IFR was tolerated in rats and mice i.v. at a 8 g/kg bw dose. The iodinated fluorinated molecule tested appears promising for the formulation of new contrast agents for diagnosis.