Scalable Terbium-149 Production from Highly Enriched Gadolinium-150 Targets

Abstract: We propose a two-stage production method to overcome existing supply-constraints for the alpha-emitter $<sup>{149\mathrm{g}}$Tb, a promising candidate for Targeted Alpha Therapy (TAT) with no existing globally scalable production pathway. Although awaiting experimental measurement of the $<sup>{150}$Gd(p,2n)$<sup>{149\mathrm{g}}$Tb cross section, the proposed method could produce $<sup>{149\mathrm{g}}$Tb at clinical scale and beyond on readily available proton cyclotrons, enabled by production of the extinct but long-lived isotope $<sup>{150}$Gd, a pure alpha emitter with a 1.79 million year half-life. Stage one generates $<sup>{150}$Gd feedstock by irradiating natural Eu or enriched $<sup>{151}$Eu with $\gtrsim$10 MeV protons, neutrons or photons. Stage two produces $<sup>{149\mathrm{g}}$Tb from fabricated $<sup>{150}$Gd targets by driving the $<sup>{150}$Gd(p,2n)$<sup>{149\mathrm{g}}$Tb reaction with $\gtrsim$14 MeV protons, accessible on over 700 reported cyclotrons worldwide. Fast fusion neutrons appear to offer the most scalable pathway for $<sup>{150}$Gd production: even with a large $^{149 \mathrm{g}}$Tb dose size of 1 GBq and 40 million administered doses/yr, we estimate this would require neutrons produced by only 6.8 megawatts of steady-state deuterium-tritium power to produce the required $<sup>{150}$Gd, far below expected capacity in the next decade. The route described here, if validated, would enable $<sup>{149\mathrm{g}}$Tb supply at the scale needed to support clinical development of $<sup>{149\mathrm{g}}$Tb-based TAT.