Patent Number: 046817271
Section: summary

BACKGROUND OF THE INVENTION The invention relates to processes for the commercially practical production of radiopharmaceutical activities and, more particularly, relates to a process for the production of astatine-211 (At-211). For about the last forty years, there has been an interest in exploring the potential of At-211 for therapeutic biomedical applications. At-211 decay results in nearly pure alpha particle emissions. The radiotoxicity associated with such alpha particle emissions and the associated emissions resulting from the decay of its daughter, polonium-211 (Po-211), which has a half-life of only about 0.56 seconds, led to early recognition of the potential for such beneficial therapeutic applications. At-211 has a half-life of 7.21 hours, which is sufficiently long to enable its practical production, chemical synthesis, transportation, quality control and appropriate biological application in a number of useful radiopharmaceutical treatments of certain diseases. Heretofore, research and development work relating to such radiopharmaceutical treatment procedures has largely focused on the preparation and in vivo evaluation of labelled antibodies, proteins, drugs and inorganic colloids. Such research has usually concentrated on the production of At-211 as a source of Astatine for studies of the physical and chemical properties of the element. In addition to the interest generated by the established and potential uses of At-211 in therapeutic radiopharmaceuticals, increasing attention is being received by At-211 due to its potential use in radiation synovectomy and for fundamental studies in cell biology. It has been demonstrated, for example, that At-211 Tellurium-colloid can be curative, without undue toxicity, in mice bearing Ascites tumor cells. Among currently available alpha particle emitters, At-211 is particularly promising for radiopharmaceutical therapeutic uses, because it decays by a double branched pathway into lead (Pb-207), directly by alpha emission, and indirectly through electron capture into polonium (Po-211), which in turn decays almost spontaneously by alpha emission. In the past, radiochemical separation of At-211 has been found to be generally unreliable due to the low and variable recovery yields attainable with such processes. If an At-211 radiopharmaceutical is to be developed for clinical application, it will be necessary to develop a production process in which small controlled volumes of At-211, in specified chemical forms, can be produced more reliably and consistently. Preferably, such a process would be readily controllable to produce desirable small volumes of selected activities in a solution of solvents that is compatible with preselected radiopharmaceutical procedures in which the activities are to be used. More specifically, it would be desirable to have such a process in which a choice of solvents can be effectively used in the production of a desired At-211 radiopharmaceutical. OBJECTS OF THE INVENTION A major object of the invention is to provide a process for reliably and consistently producing an At-211 radiopharmaceutical in a desirably small controllable volume. Another object of the invention is to produce an At-211 radiopharmaceutical by a process that includes the option of eluting At-211 with a choice of solvents, any of which are compatible with subsequently desired radiopharmaceutical procedures in which the At-211 radiopharmaceutical is to be utilized. A further object of the invention is to provide a process for reliably producing an At-211 radiopharmaceutical in the chemical form as Astatide and in a desirably small controlled volume. Still another object of the invention is to provide a process that utilizes a novel one-step distillation and collection procedure for producing At-211. Yet another object of the invention is to provide a process for isolation of At-211 by distilling it from a heated bismuth target that has been irradiated with alpha particles, collecting the vapor condensate in a silica gel, and eluting At-211 from the silica gel with a controllable volume of eluent that contains a solvent, which is preselected to be compatible with a given radiopharmaceutical procedure in which the At-211 is to be used. A still further object of the invention is to provide a process for isolating At-211 from a Bismuth target without requiring the use of other chemicals, which frequently are a source of contaminants, thereby to avoid the introduction of contaminants into the isolated At-211. Another object of the invention is to provide a process for isolating At-211, wherein the vaporization of bismuth from a target is suppressed by using a selected choice of dry carrier gases, which is effective to prevent Bi metal from contaminating the At-211 isolated by the process. Additional objects and advantages of the invention will become apparent to those skilled in the art from the description of it presented herein, considered in conjunction with the accompanying drawings. SUMMARY OF THE INVENTION In one preferred arrangement of the invention a At-211 radiopharmaceutical is produced by a process in which a target of irradiated bismuth is heated within a critical range of temperatures, for a predetermined period of time, in a suitable still, while passing a dry carrier gas through the still to carry At-211 vapor evolved from the Bi target to a condenser which has a condensate collector that is effective to remove essentially all of the At-211 from the carrier gas. Subsequently, as a safety precaution, the carrier gas is passed through a series of filters to remove remaining traces of the At-211 from it. A small controlled volume of eluent, which is preselected from a choice of solvents, is used to elute At-211 from the condensate collector. Finally, the controlled volume of eluent containing the At-211 is eluted from the condensate collector and held for use in a selected radiopharmaceutical procedure.