(331d) Diglycolamide (DGA) - Functionalized Membrane Adsorbers for Upstream Radiopharmaceutical Purification

Ac-225 is a promising isotope for targeted alpha therapy that has shown excellent patient outcomes in clinical trials. Historically, Ac-225 used in domestic clinical trials was harvested from legacy nuclear waste at Oak Ridge National Laboratory. This legacy supply of Ac-225 was so limited that only 1 in 5,500 people who qualified for the treatment were able to receive it. Now, Ac-225 is produced and purified at Brookhaven National Laboratory in a linear accelerator, BLIP. Scaling up the production and purification process requires new separation materials that can operate at higher productivities. While resin-based extractive chromatography has long been the workhorse for medical isotope production—these purification schemes are not easily scaled to support clinically relevant production. The final polishing step requires ion-ion selectivity between Ac-225 (a trivalent actinide) and trivalent lanthanide fission products; thus highly-selective and rapid-separation materials and processes are required.

To fill this need, we synthesized chelating membrane adsorbers—a scalable, high-throughput alternative to extractive resins. Electrospun poly(chloromethyl styrene membranes) were functionalized with a linear diglycolamide (DGA) ligand through an SN2 reaction. The resulting membranes contained 36wt% DGA which is consistent with commercially available extractive resins containing physisorbed DGA ligands. After functionalization the membranes maintain a high permeance of ~ 500 LMH/bar. Adsorption experiments modeled with the Langmuir isotherm indicate 1) DGA retains is affinity when covalently bound and 2) the membrane capacity is an order of magnitude lower than the resin capacity for lanthanides. Adsorption and desorption experiments were performed using Ac-225 at Brookhaven National Laboratory. Rapid desorption kinetics suggest that these DGA-functionalized membranes have the potential to accelerate the Ac-225 purification process. Direct comparisons will be made to the commercially available DGA extractive resin which is the current state of the art. While these chelating membranes are being studied in the context of nuclear medicine, they serve as a promising platform for other applications which require ion-ion selectivity such as rare earth element recovery and radioanalytical chemistry.