SELECTIVE OPACIFICATION OF LIVER.

DIAGNOSIS OF SMALL LIVER TUMORS IS USUALLY DIFFICULT BY CONVENTIONAL X-RAY, EVEN WHEN AIDED BY CT. ADMINISTRATION OF AN INTRAVENOUS CONTRAST AGENT CONSISTING OF EMULSIFIED IODINATED OIL PROVIDES EXCELLENT CONTRASTS OF LIVER TUMORS WITH MINIMAL TOXICITY. THE PRODUCT, HOWEVER, IS MADE IN LABORATORY SCALE USING RELATIVELY UNCHARACTERIZED EMULSIFIERAND SMALL HOMOGENIZING BOTTLES WITH EMPIRICALLY DEFINED HOMOGENIZING PARAMETERS. THE PRODUCT IS AVAILABLE ONLY FOR INVESTIGATIONAL USE, AND SCALING UP TO COMMERCIAL SCALE IS NEEDED IF THIS AGENT IS TO BECOME AVAILABLE FOR ROUTINE USE.THIS CONTRACT PROPOSES TO CONDUCT RESEARCH TOWARDS THE DEVELOPMENT OF A TECHNOLOGY FOR PREPARATION OF SIMILAR PRODUCT(S) IN LARGE QUANTITIES FOR COMMERCIAL USE. PHASE I OF THE PROJECT WILL CONSIST OF (1) CHARACTERIZING AND STANDARDIZING THE EMULSIFIER (PREFERABLY OF NATURAL ORIGIN) AND (2) ATTEMPTING THE LABORATORY SCALE EMULSIFICATION PROCESS IN CONTINUOUS FLOW TYPE APPARATI SUCH AS HIGH- PRESSURE ORIFICE MILLS OR COLLOID MILLS. THE REPRODUCI- BILITY OF THE GLOBULE SIZE DISTRIBUTION WILL BE EVALUATED USING ELECTRONIC PARTICLE COUNTERS. IODINATED OIL TO BE EMULSIFIED WOULD BE IODINATED ESTER OF POPPY SEED OIL. SUCCESSFUL IDENTIFICATION OF EMULSIFIER AND FEASIBILITY OF SUITABLE EMULSIFYING INSTRUMENTS WILL LEAD TO PHASE II, WHICH WOULD CONSIST OF (1) IDENTIFYING AND ASSURING A SOURCEOF IODINATED OIL; (2) SCALING UP OF THE LABORATORY SCALE OPERATION; (3) EVALUATION OF PRESERVATIVES AND/OR TERMINAL STERILIZABILITY; (4) LONG-TERM STABILITY OF THE PRODUCT; AND(5) ANIMAL STUDIES TO DETERMINE TOXICITY AND OPTIMAL GLOBULESIZE OF THE EMULSION. PHASE II MAY ALSO CONSIST OF LIMITED CLINICAL STUDIES.