Development of a unique bismuth (Bi-213) automated generator for use in cancer therapy

A unique separations chemistry and an automated "generator" have been devel oped for application of the alpha-emitting radionuclide Bi-213 to cancer th erapy. The generator was developed for separation of the short-lived Bi-213 (t(1/2) = 45.6 min) from the parent radionuclide Ac-225 (t(1/2) = 10 days) , which is separated from Th-229 (t1/2 = 7340 yr) and its daughter isotope Ra-225 (t(1/2) = 14.8 days). The generator requires purified Ac-225 and use s organic anion-exchange system capable of isolating Bi-213 from a HCl solu tion of Ac-225. Th, anion resin is then washed and stripped of the Bi produ ct using a sodium acetate buffer. This allows direct attachment of Bi-213 t o modified monoclonal antibodies and other targeting agents for use in pati ent treatment of cancers such as leukemia. To permit safe and rapid isolati on of Bi-213 in 1 to > 20 mCi quantities, an automated system using sequent ial flow injection was developed. Successful evaluation of the labeling eff iciency of proteins was completed using the separated Bi product.