Pharmaceutical Corporation in San Diego; however, the opinion expressed here are solely his and not necessarily those of the Corporation. Jean G. Riess received his chemical engineer and doctorat-e `s-sciences degrees (the latter with Professor Guy Ourisson in 1963) from the University of Strasbourg. He then spent two years with John Van Wazer at Monsanto in Saint-Louis, MO, learning some phosphorus and transitionmetal chemistry. In 1968 he became Professor at the University of Nice, France, where he founded, directed, and eventually became honorary director of the Unite ´de Chimie Mole ´culaire (associated with the Centre National de la Recherche Scientifique). His research successively involved phosphorus chemistry, transition-metal chemistry, organometallics, and eventually perfluorochemicals. His present interests are in fluorocarbons, fluorinated amphiphiles, and their colloid chemistry, including fluorocarbon emulsions for in vivo O 2 delivery, fluorinated self-assemblies, and drug delivery systems. Professor Riess has published about 360 papers and holds ca. 25 patents. He has served on numerous councils and committees and has chaired or co-chaired international conferences on phosphorus chemistry and blood substitutes. He has won awards from the French Academy of Sciences, French Chemical Society, Alexander von Humboldt Stifftung, City of Nice and Controlled Release Society, as well as Alliance's first Distinguished Contribution Award. He holds an honorary Research Associate position at the University of California at San Diego and sits on the Board of Directors of Alliance Pharmaceutical Corp.

Ultrasonography has, until recently, lacked effective contrast-enhancing agents. Micrometer-sized gas bubbles that resonate at a diagnostic frequency are ideal reflectors for ultrasound. However, simple air bubbles, when injected into the blood stream, disappear within seconds through the combined effects of Laplace pressure, blood pressure, and exposure to ultrasound energy. Use of fluorocarbon vapor, by extending the persistence of microbubbles in vivo from seconds to minutes, propelled contrast ultrasonography into clinical practice. Imaging techniques that selectively suppress tissue, but not microbubble signal, further increase image contrast. Approved products consist of C3F8 or SF6 microbubbles, and N2 microbubbles osmotically stabilized with C6F14. These agents allow the detection and characterization of cardiovascular abnormalities and solid organ lesions, such as tumors. By providing higher quality images, they improve the accuracy and confidence of disease diagnosis, and can play a decisive role in clinical decision making. New objectives include agents that target specific cells for the molecular imaging of disease, and drug and gene delivery, including ultrasound-triggered delivery.

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The unique behavior of perfluorocarbons (PFCs), including their high oxygen dissolving capacity, hydrophobic and lipophobic character, and extreme inertness, derive directly, in a predictable manner, from the electronic structure and spatial requirements of the fluorine atom. Their low water solubility is key to the prolonged in vivo persistence of the now commercially available injectable microbubbles that serve as contrast agents for diagnostic ultrasound imaging. Oxygent, a stable, small-sized emulsion of a slightly lipophilic, rapidly excreted PFC, perfluorooctyl bromide (perflubron), has been engineered. Significant oxygen delivery has been established in animal models and through Phase II and III human clinical trials. However, an inappropriate testing protocol and the lack of funding led to temporary suspension of the trials.

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The basic properties of perfluorocarbons (PFCs) and PFC emulsions relevant to their use as oxygen delivery systems are briefly reviewed. The key issues related to the selection of an appropriate, readily excretable PFC and the engineering of a stable injectable PFC emulsion are discussed. Oxygent, a terminally heat-sterilized, injectable 60% w/v PFC emulsion made primarily of F-octyl bromide and a few percent of F-decyl bromide, with egg phospholipids as an emulsifier, has been developed. Its efficacy in avoiding and reducing red cell transfusion during surgery has been established during a Phase III clinical evaluation. Another Phase III clinical trial in cardiopulmonary bypass surgery, with a protocol that included both augmented-acute normovolemic hemodilution and intraoperative autologous donation, has, however, been interrupted following the observation of adverse events. Data analysis assigned these events to an inappropriate study protocol. A search for possible interactions between Oxygent and fluids present during cardiopulmonary bypass surgery detected no effect of the emulsion on hemostasis, hemolysis and blood rheology.