Ultrasonic visualization of perfluorocarbons (PFC's) marks the first time that tissue echogenicity has been persistently altered following the intravenous administration of a contrast agent. PFC's are organic compounds where each hydrogen atom has been replaced by fluorine. PFC'S are administered intravenously in an emulsion form. Preliminary studies have shown that two PFC's perfluoroctylbromide (PFOB), the only radiopaque PFC nearing clinical trials, and Fluosol DA 20% (Fluosol), the only PFC used in human subjects serve as echogenic contrast agents for the selective marked enhancement of the normal liver and spleen and produce an intense echogenic rim around VX2 tumor nodules allowing their recognition from normal intrahepatic structures. The proposed projects will be conducted utilizing laboratory animals to answer or give insight into the following: 1) The reasons for the ultrasonic visualization of PFC by assessing the acoustic property both in vitro and in vivo of the liver with and without PFC; 2) Assess whether there is an increase in the number of macrophages within the tumor nodule following PFC administration by measuring the radioactivity of the tumor nodules obtained from PFC treated and non-treated animals after the reinjection of homologous Indium111 labelled peritoneal white cells; 3) Assess the increase in sensitivity in detecting hepatic tumors in rabbits with multiple diffuse liver tumors before and after PFC by assessing the number of tumor nodules seen prior to and following the administration of PFC. Fluosol is being tested clinically for the treatment of anemia and ischemic brain and heart disease, as an oxygen carrying blood expander. Extensive toxicity studies are already available, indicating its relative safety in human subjects. The proposed research project in humans will evaluate the effect of Fluosol as an ultrasound contrast agent in man, establish the optimal human dose to produce liver and splenic enhancement, and the optimum time to scan following PFC administration. This will be accomplished in patients with known liver tumors by monitoring the changes in the echogenicity of the tumor, liver and spleen following PFC administration.
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