Compared to the solid target production, the solution target approach leads to lower radionuclide yields but has an advantage of being more amenable to automation. Recently, the production of 68Ga in liquid targets from enriched 68Zn salt solutions has been described, using either ZnCl 2 or Zn(NO 3) 2. However, the cyclotron production of 68Ga in solid targets from 68Zn and its subsequent separation require either installation of expensive automated solid target systems or requires a series of manual pre- and post-irradiation target handlings. Since many PET-centers have their own cyclotrons, this is potentially a convenient means of in-house production of 68Ga-tracers. An alternative method of 68Ga production is the irradiation of 68Zn using a cyclotron. Meeting the growing demand for 68Ga is a challenge, as it is mostly supplied by the gallium generators which suffer from high prices, long lead time, quality inconsistencies, and limited shelf life. The easy chelation chemistry and convenience of 68Ge/ 68Ga-generators further contribute to 68Ga popularity in clinical and pre-clinical settings. In recent years Ga-HBED-PSMA-11, a 68Ga-labeled PSMA (prostate-specific membrane antigen) ligand emerged as the gold standard for prostate cancer diagnostics, driving a high adoption rate of 68Ga in clinics. The advancement of positron emission tomography (PET) and FDA’s approval of Ga-DOTA-TATE (Netspot®) moved gallium-68 ( 68Ga, t 1/2 = 68 min) to the forefront of neuroendocrine tumor diagnostics. For years, gallium-67 ( 67Ga, t 1/2 = 78 h) scintigraphy has been a linchpin of molecular imaging of cancer, including non-Hodgkin’s lymphoma, Hodgkin’s disease, as well as various infections. Radiogallium ( 66,67,68Ga = *Ga) has a long and notable history in nuclear medicine. Using HGaCl 4 and ZnCl 2 as the extractable species, the COSMO-RS theory predicts the solvation-driven extraction of Ga and Zn with a mean unsigned error of prediction of 4.0% and 3.4% respectively. The process did not extract Cu, Mn, and Co but did extract Fe. TFT plays a key role in controlling the interfacial tension between the aqueous and the organic phases, ensuring clean membrane-based separation. From 1 M ZnCl 2/6 M HCl, a 1/2 (v/v) n-butyl methyl ether ( n-BuOMe)/TFT solvent extracts 95.7 ± 2.0% of *Ga and 0.005 ± 0.003% of Zn in flow. From 5.6 M ZnCl 2/3 M HCl, a 1/2 (v/v) diisopropyl ether ( iPr 2O)/trifluorotoluene (TFT) solvent extracts 76.3 ± 1.9% of *Ga and 1.9 ± 1.6% of Zn in flow using a single pass through. Herein we report efficient extraction of radiogallium ( 66,67,68Ga = *Ga) from ZnCl 2/HCl solutions in batch and in flow using a membrane-based liquid-liquid separator. A switch from batch to continuous manufacturing of gallium-68 ( 68Ga) and 68Ga-labeled pharmaceuticals can be advantageous, as it recycles isotopically-enriched zinc-68 ( 68Zn), removes pre- and post-irradiation target manipulations, and provides scalability via dose-on-demand production.
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