High Specific Activity Sm-153 By Post Irradiation Isotope Separation (Final Scientific Technical Report)

The isotope, samarium-153 (153Sm) has ideal nuclear properties well suited for a variety of therapeutic applications; however, it is only available with low specific activity (radioactivity per unit mass) due to the method of production. Commercially useful quantities can be made by the 152Sm (n,γ) 153Sm reaction in a nuclear reactor, but typical irradiation parameters result in less than 2% of the 152Sm target material being converted, leading to a very diluted end product. Since chemical processing methods cannot be used to perform isotopic separation, this means that >98% of the resultant pharmaceutical molecules are labeled with “cold” target atoms and are incapable of providing any radiation-induced therapeutic effect. The goals of this project were to introduce a new approach to the production of high specific activity (HSA) 153Sm utilizing electromagnetic isotope separation (EMIS), and to perform biodistribution and chemistry studies with such HSA 153Sm to test labeling capability with targeting molecules. Included in these studies was the successful development of a collection substrate that would allow the efficient deposit and removal of 153Sm; to this end, DLC (diamond like carbon) foils were successfully employed. In the first year of this project a surface ion source was developed, leading to the successful production of a mass separated beam of stable Sm ions. Studies were then performed using similar apparatus at the Oak Ridge National Laboratory, leading to a well-separated beam of isotopically pure samarium ions. This was followed by the successful production of four 15 mCi samples (over a 7 month period) of HSA 153Sm which were delivered to the IsoTherapeutics Group for biodistribution and chemical labeling studies. Such samples were produced by neutron irradiation of 5 mg metal samples of 152Sm at the HFIR (ORNL High Flux Isotope Reactor), followed by manual transfer of the samples from the irradiation capsule to the chamber of a surface ion source. Isotopic beams were then extracted using the IRIS2 EMIS facility, and collected onto 10 μm thick DLC foils. The samples were irradiated for 10 h periods, with typical collection periods lasting 12 - 16 h. Employing appropriate chemical approaches, these HSA 153Sm samples were evaluated for labeling with small, medium and large molecules. The ability to label a variety of targeting molecules is important to demonstrate the potential therapeutic capabilities. Biodistribution studies, using HSA 153Sm with the bone agent DOTMP, in rodents demonstrated that the biodistribution is similar to what is observed with LSA 153Sm. Labeling was successfully achieved with peptides, and large protein molecules.