Recovery of Gallium-68 and Zinc from HNO(3)-Based Solution by Liquid–Liquid Extraction with Arylamino Phosphonates

The cyclotron production of gallium-68 via the (68)Zn(p,n)(68)Ga nuclear reaction in liquid targets is gaining significant traction in clinics. This work describes (1) the synthesis of new arylamino phosphonates via the Kabachnik–Fields reaction, (2) their use for liquid–liquid extraction of (68)Ga from 1 M Zn(NO(3))(2)/0.01 M HNO(3) in batch and continuous flow, and (3) the use of Raman spectroscopy as a process analytical technology (PAT) tool for in-line measurement of (68)Zn. The highest extraction efficiencies were obtained with the extractants functionalized with trifluoromethyl substituents and ethylene glycol ponytails, which were able to extract up to 90% of gallium-68 in batch and 80% in flow. Only ppm amounts of zinc were co-extracted. The extraction efficiency was a function of pKa and the aqueous solubility of the extractant and showed marked concentration, solvent, and temperature dependence. Raman spectroscopy was found to be a promising PAT tool for the continuous production of gallium-68.