Compositions And Methods For Enhancing Contrast In Imaging

Abstract

Example compositions of liposomes with hydrophilic polymers on their surface, and containing relatively high concentrations of contrast-enhancing agents for computed tomography are provided. Example pharmaceutical compositions of such liposomes, when administered to a subject, provide for increased contrast of extended duration, as measured by computed tomography, in the bloodstream and other tissues of the subject. Also provided are example methods for making the liposomes containing high concentrations of contrast-enhancing agents, and example methods for using the compositions.

1 - 17 . (canceled) 
     
     
         18 . A method for making a composition, comprising:
 selecting one or more solutions containing one or more nonradioactive contrast-enhancing agents; and   forming sterically stabilized liposomes in the presence of the one or more solutions containing one or more nonradioactive contrast-enhancing agents to provide a solution of sterically stabilized liposomes that is associated with the one or more nonradioactive contrast-enhancing agents.   
     
     
         19 . The method of  claim 26 , wherein the concentrating comprises one or more of: (i) precipitating at least some of the nonradioactive contrast-enhancing agents from the solution containing one or more nonradioactive contrast-enhancing agents and suspending the precipitated nonradioactive contrast-enhancing agents in a liquid at a higher concentration, and (ii) evaporating at least some of a liquid from the solution containing one or more nonradioactive contrast-enhancing agents. 
     
     
         20 . The method of  claim 18 , further comprising concentrating the solution of sterically stabilized liposomes that is associated with the one or more nonradioactive contrast-enhancing agents to produce a more concentrated solution of sterically stabilized liposomes that is associated with the one or more nonradioactive contrast-enhancing agents, the more concentrated solution of sterically stabilized liposomes that is associated with the one or more nonradioactive contrast-enhancing agents containing from about 37 to about 200 milligrams of iodine per milliliter of the more concentrated solution of sterically stabilized liposomes that is associated with the one or more nonradioactive contrast-enhancing agents. 
     
     
         21 . The method of  claim 20 , wherein the step of concentrating the solution of sterically stabilized liposomes that is associated with the one or more nonradioactive contrast-enhancing agents to produce a more concentrated solution of sterically stabilized liposomes that is associated with the one or more nonradioactive contrast-enhancing agents comprises one or more of, dewatering, ion exchange, washing, and dialysis. 
     
     
         22 . The method of  claim 18 , wherein forming the sterically stabilized liposomes comprises one or more of:
 hydrating dried lipids in the presence of the one or more solutions containing one or more nonradioactive contrast-enhancing agents;   mixing a volatile organic solution of lipids with the one or more solutions containing one or more nonradioactive contrast-enhancing agents; and   dialyzing an aqueous solution of one or more of lipids, detergents, and surfactants in the presence of the one or more solutions containing one or more nonradioactive contrast-enhancing agents to remove the one or more lipids, detergents, and surfactants.   
     
     
         23 - 25 . (canceled) 
     
     
         26 . The method of  claim 18 , further comprising concentrating at least one of the solutions containing one or more nonradioactive contrast-enhancing agents by at least about 10% to produce a concentrated solution of nonradioactive contrast-enhancing agents. 
     
     
         27 - 37 . (canceled) 
     
     
         38 . A method comprising:
 selecting one or more nonradioactive contrast-enhancing agents; and   forming sterically stabilized liposomes in the presence of the nonradioactive contrast-enhancing agents to provide liposomes containing or associated with one or more contrast-enhancing agents.   
     
     
         39 . The method of  claim 38 , where one milliliter of a suspension of the sterically stabilized liposomes has at least 30 milligrams of iodine. 
     
     
         40 . The method of  claim 38 , where an average diameter of the sterically stabilized liposomes is less than about 120 nanometers. 
     
     
         41 . The method of  claim 38 , where liposomes are found in the presence of one or more contrast-enhancing agents using a method selected from the group consisting of hydration of dried lipids in the presence of one or more contrast-enhancing agents, mixing a volatile organic solution of lipids with an aqueous solution of one or more contrast-enhancing agents causing evaporation of the organic solution, and dialysis of an aqueous solution of lipids and detergents and/or surfactants to remove the detergents and/or surfactants and form liposomes in the presence of one or more contrast-enhancing agents. 
     
     
         42 . A method comprising:
 forming sterically stabilized liposomes; and   drawing one or more nonradioactive contrast-enhancing agents into the liposomes to provide liposomes containing or associated with one or more contrast-enhancing agents.   
     
     
         43 . The method of  claim 42 , where one milliliter of a suspension of the sterically stabilized liposomes has at least 30 milligrams of iodine. 
     
     
         44 . The method of  claim 42 , where an average diameter of the sterically stabilized liposomes is less than about 120 nanometers.