Development of an in vivo generator for alpha emitters: the ²²⁵Ac/²¹³Bi system

Full text of publication follows. Background: Actinium-225 (t_1/2=10 d) decays by α-emission with 3 α-emitting daughters including the α-emitter ²¹³Bi (t_1/2=46 min). Both ²²⁵Ac as an in-vivo generator and ²¹³Bi have been successfully utilized in alpha radioimmunotherapy clinical research and trials. Current production of ²²⁵Ac from decay of long-lived ²²⁹Th is very limited. In this paper we report results of the first production of a small batch of ²²⁵Ac by an alternative method of direct production via high energy proton spallation reaction on natural thorium. Methods: Target design and irradiation were performed at BNL. Chemical processing of the irradiated Th foils was developed at ORNL. Encapsulation of natural Th foils (Goodfellow) was carried out in a glove box under Helium atmosphere. Disks of Th foils (25.4 * 0.125 mm) were individually wrapped in 0.0254 mm Al foil (to prevent contamination), and packed into an Al target holder sandwiched between an Al monitor foil (0.508 mm) upstream and a Cu disk (3.42 mm thick). Proton irradiation was conducted at incident Linac energy of 138.5 MeV with energy degradation in Th foils 129.1→128.1 MeV, for 107.4 h at an effective current of 45.2 μA. The irradiated foils were shipped to ORNL after 3 days of decay. Results and discussion: Yield of ²²⁵Ac at EOB from a Th foil (166 mg/cm²) was (10.5 ± 0.6)mCi (2.2x10^-3 mCi/μA-h). This value is about 7% higher than yield predicted based on reported excitation functions (Refs 1,2). At EOB, ²²⁷Ac impurity was ∼ 0.13% of ²²⁵Ac. To scale up the production, thicker targets with larger diameter are being developed. References: 1] Weidner J. W., et al. Applied Radiation and Isotopes 70, 2602 (2012); 2] Ermolaev S. V., et al. Radiochimica Acta 100, 223 (2012). (authors)