Membrane Separation of Cu-67 for Use in Theranostics

Because of its β^− and γ decay routes, ⁶⁷Cu is a very promising radioisotope for use in theranostic cancer treatments. Currently, ⁶⁷Cu is produced through the irradiation of either ⁶⁸Zn or ⁶⁷Zn in a cyclotron, a traditional nuclear reactor or a linear electron accelerator. Once formed, a small amount of copper (nanograms) has to be separated from the large amount of remaining zinc (grams) and undesired byproduct isotopes such as ⁶⁶Ga, ⁶⁷Ga, ⁶⁴Cu, ⁶¹Cu, ⁵⁸Co. Currently, such separations are performed in resin-packed columns and can require 3–4 h to purify a 5 g target. These procedures may involve multiple columns and require the target to be dissolved and reconstituted several times in different solutions and concentrations of acids. The complexity and length of resin-based separations combined with the 2.58-day half-life of ⁶⁷Cu has caused a shortage of ⁶⁷Cu for research and clinical trials.

Compared to resin-packed columns, membrane adsorbers have been shown to decrease processing times in pharmaceutical production. Transport through membrane adsorbers is not limited by diffusion limited; therefore, they can be operated at a higher flow rates than resin-packed columns. In this work, we design new membrane adsorbers from the ground-up with the goal of simplifying the purification process and reducing the number of steps needed for separation. Poly(glycidyl methacrylate) (GMA) brushes are grown from polyvinylidene fluoride membranes using activators are generated by electron transfer Atom transfer radical polymerization (AGET ATRP), a controlled polymerization technique. The epoxide ring of the GMA monomer can be opened by a nucleophile when heated. This approach was employed to covalently attach ethylene diamine (ED) and putrescine groups to the polymer brush. We hypothesize that the ligands will have different affinities for copper to our PVDF-pGMA membranes. The polymerization reaction time was varied between 30 min to 12 h and under different ratios of reducing agent (ascorbic acid) to Cu(II). The degree of grafting has been approximated using peak ratios obtained with FTIR where a high ratio is associated with greater degree of grafting. Pure water permeability tests reflect the expected inverse relationship between degree of grafting and permeability. Static binding tests are underway to determine total membrane uptake from pH 2 HCl. In the future, dynamic binding tests will determine the “on column” separation performance of the membranes.