The cyclotron production of gallium-68 via the 68Zn(p,n)68Ga 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 68Ga from 1 M Zn(NO3)2/0.01 M HNO3 in batch and continuous flow, and (3) the use of Raman spectroscopy as a process analytical technology (PAT) tool for in-line measurement of 68Zn. 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.
Keywords: arylamino phosphonate; cyclotron production of gallium-68; gallium-68; liquid target; liquid–liquid extraction.