Development of ²²⁵Ac/²¹³Bi generator based on α-ZrP-PAN composite for targeted alpha therapy

Radioligand therapy using alpha emitters has gained more and more prominence in the last decade. Despite continued efforts to identify new appropriate radionuclides, the combination of ²²⁵Ac/²¹³Bi remains among the most promising. Bismuth-213 has been employed in clinical trials in combination with appropriate vectors to treat patients with various forms of cancer, such as leukaemia, bladder cancer, neuroendocrine tumours, melanomas, gliomas, or lymphomas. However, the half-life of ²¹³Bi (T_½ = 46 min) implies that its availability for clinical use is limited to hospitals possessing a ²²⁵Ac/²¹³Bi radionuclide generator, which is still predominantly scarce. We investigated a new Ac/Bi generator system based on using the composite sorbent α-ZrP-PAN (zirconium(IV) phosphate as active component and polyacrylonitrile as matrix). The developed ²²⁵Ac/²¹³Bi generator was subjected to long-term testing after its development. The elution profile was determined and the elution yield, the contamination of the eluate with the parent ²²⁵Ac and the contamination of the eluate with the column material were monitored over time.

The high activity (75 MBq of parent ²²⁵Ac) generator with a length of 75 mm and a diameter of 4 mm containing the composite sorbent α-ZrP-PAN with a particle size of 0.8 to 1.0 mm as the stationary phase, eluted with a mixture of 10 mM DTPA in 5 mM nitric acid, provided ²¹³Bi with yields ranging from 77 % to 96 % in 2.8 mL of eluate, with parent ²²⁵Ac contamination in the order of 10^-3 %, up to twenty days of use.

All the results of the monitored parameters indicate that the composite sorbent α-ZrP-PAN based separation system for the elution of ²¹³Bi is a very promising and functional solution.