Project Title: Increasing Astatine-211 Production through Target Design and Automated Isolation D. Scott Wilbur, Ph.D., Lead Principal Investigator, University of Washington (Lead Institution) Kristian Myhre, Ph.D. Co-Principal Investigator, Oak Ridge National Laboratory Lane Carasik, Ph.D., Co-Principal Investigator, Virginia Commonwealth University

Astatine-211( 211At)-labeled cancer therapy agents have tremendous potential for treating cancer, particularly blood-borne and metastatic cancers. However, at present there are a limited number of sites in the US that can produce 211At, so it is important to produce as much 211At as possible at each site. This research effort will examine approaches to make the alpha-emitting radionuclide 211At more widely available to the U.S. research and medical community through improvement of production methods. 211At has a short half-life (7.2 h) and is produced by irradiation of bismuth metal with an alpha-particle beam. The short half-life makes it imperative that it be produced at or near a clinical site where it will be used. Another factor that limits its availability is the bismuth target material. Because bismuth has a low melting point (271°C) and has poor thermal conductivity it is difficult to irradiate with the high alpha beam currents required for production of higher quantities of 211At. Also, the method of isolation of 211At from bismuth targets can limit the amount isolated and available for use. Thus, the goals of the research effort are to improve the thermal properties of Bi targets and automate the recovery of 211At from those targets. These goals will be accomplished through three specific objectives conducted in a collaboration of researchers at the University of Washington, the Oak Ridge National Laboratory and the Virginia Commonwealth University. An additional objective is to train student/postdoctoral fellows in aspects of radionuclide production. The specific objectives of the project include: (1) the design of novel targets that can withstand high a-beam currents through 3D modeling of heat transfer in various configurations of target holders and target materials; (2) fabrication and testing of target holders and bismuth target materials for increased heat transfer; evaluating 211At production rates; and analyzing irradiated target materials; (3) evaluating automated isolation of 211At from the new target designs and testing 211At radiolabeling to demonstrate its utility; and (4) training students and postdoctoral fellows/scholars in thermal modeling, radiochemical methods and radionuclide production, including targetry and automation of radionuclide isolation. Success in obtaining bismuth targets with higher thermal conductivity will result in an ability to produce more 211At for the development of new cancer treatment agents and for clinical trials to evaluate those agents