A Novel Radium-Selective Separation Technique to Improve the Production of 225Ac for Cancer Immunotherapy

225Ac is valuable isotope for radioimmunotherapy treatment of cancers by means of targeted alpha therapy (TAT) However, the production capacity for it is currently insufficient to support the clinical- and commercial-scale demand for TAT drugs This proposal describes a process for facilitating production of 225Ac by providing source material in the form of the radium isotopes (primarily 228Ra) that could become a key precursor in the pathway for efficient production of 225Ac RadTran has developed a highly selective, high-yield, simple, scalable, and environmentally conscious process for collecting radium The separation technique is a variant of molecular recognition technology occurring in a nonconventional chromatography setting This proposal describes how this technology will be applied to collect 228Ra from natural thorium and thereby provide material for neutron irradiation-based production of 229Th (the precursor to 225Ac) Phase 1 will focus on isolating 228Ra from a bulk natural thorium (232Th) nitrate solution Pre-phase 1 proof of concept has thus far focused on understanding the potential for this technology to extract radium at very low concentration from a bulk 232Th stock, and how contaminants (or 232Th itself) may challenge this extraction Column trials have been conducted with a spiked radium concentration more than an order of magnitude lower than we expect from the 232Th solution, and thereby established the basic affinity and kinetic requirements for efficient (>96%) radium extraction via this method Phase 1 will continue proof of concept by determining the effect that specific thorium nitrate solution contaminants have on radium extraction The contaminants include natural and radiogenic elements that are known to have affinities for the separation chemistry Characterizing these effects comprehensively and quantitatively will ultimately be crucial for the extraction efficiency Phase 1 proof of concept will also include column trails in a “micro-pilot plant” utilizing the same 232Th nitrate solution to be used in a scaled up or commercial production plant Column loading, column saturation, column reusability and radium recovery will be demonstrated as part of this Phase 1 component The composition of the final 228Ra product will also be examined carefully Furthermore, an extensive set of computational tools will be developed to aid in the specifications of the “micro-pilot plant” These tools will be the basis of directing scalability and economic justification for the process in future stages of development A computational demonstration will justify the utility of 228Ra to produce 229Th by calculating a realistic conversion rate based on the composition of the 228Ra product and measured cross-sectional data Phase 2 will utilize the knowledge gained in Phase 1 to perform scalability testing The scalability testing is considered to be one step removed from the development of a pilot plant that is capable of supplying enough 228Ra to support clinical trial needs for 225Ac