Separation of Radiogallium from Zinc Using Membrane-Based Liquid-Liquid Extraction in Flow: Experimental and COSMO-RS Studies

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@article{7943aa5844474aa1aab26693c4836dc3,
title = "Separation of Radiogallium from Zinc Using Membrane-Based Liquid-Liquid Extraction in Flow: Experimental and COSMO-RS Studies",
abstract = "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. Herein we report efficient extraction of radiogallium (66,67,68Ga = *Ga) from ZnCl2/HCl solutions in batch and in flow using a membrane-based liquid-liquid separator. From 5.6 M ZnCl2/3 M HCl, a 1/2 (v/v) diisopropyl ether (iPr2O)/trifluorotoluene (TFT) solvent extracts 76.3 ± 1.9{\%} of *Ga and 1.9 ± 1.6{\%} of Zn in flow using a single pass through. From 1 M ZnCl2/6 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. TFT plays a key role in controlling the interfacial tension between the aqueous and the organic phases, ensuring clean membrane-based separation. The process did not extract Cu, Mn, and Co but did extract Fe. Using HGaCl4 and ZnCl2 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.",
keywords = "Gallium-68, Gallium-67, Liquid extraction in flow, COSMO-RS",
author = "Pedersen, {Kristina S{\o}borg} and Nielsen, {Karin Michaelsen} and Jesper Fonslet and Mikael Jensen and Fedor Zhuravlev",
year = "2019",
doi = "10.1080/07366299.2019.1646982",
language = "English",
volume = "37",
pages = "376--391",
journal = "Solvent Extraction and Ion Exchange",
issn = "0736-6299",
publisher = "Taylor & Francis Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Separation of Radiogallium from Zinc Using Membrane-Based Liquid-Liquid Extraction in Flow: Experimental and COSMO-RS Studies

AU - Pedersen, Kristina Søborg

AU - Nielsen, Karin Michaelsen

AU - Fonslet, Jesper

AU - Jensen, Mikael

AU - Zhuravlev, Fedor

PY - 2019

Y1 - 2019

N2 - 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. Herein we report efficient extraction of radiogallium (66,67,68Ga = *Ga) from ZnCl2/HCl solutions in batch and in flow using a membrane-based liquid-liquid separator. From 5.6 M ZnCl2/3 M HCl, a 1/2 (v/v) diisopropyl ether (iPr2O)/trifluorotoluene (TFT) solvent extracts 76.3 ± 1.9% of *Ga and 1.9 ± 1.6% of Zn in flow using a single pass through. From 1 M ZnCl2/6 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. TFT plays a key role in controlling the interfacial tension between the aqueous and the organic phases, ensuring clean membrane-based separation. The process did not extract Cu, Mn, and Co but did extract Fe. Using HGaCl4 and ZnCl2 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.

AB - 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. Herein we report efficient extraction of radiogallium (66,67,68Ga = *Ga) from ZnCl2/HCl solutions in batch and in flow using a membrane-based liquid-liquid separator. From 5.6 M ZnCl2/3 M HCl, a 1/2 (v/v) diisopropyl ether (iPr2O)/trifluorotoluene (TFT) solvent extracts 76.3 ± 1.9% of *Ga and 1.9 ± 1.6% of Zn in flow using a single pass through. From 1 M ZnCl2/6 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. TFT plays a key role in controlling the interfacial tension between the aqueous and the organic phases, ensuring clean membrane-based separation. The process did not extract Cu, Mn, and Co but did extract Fe. Using HGaCl4 and ZnCl2 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.

KW - Gallium-68

KW - Gallium-67

KW - Liquid extraction in flow

KW - COSMO-RS

U2 - 10.1080/07366299.2019.1646982

DO - 10.1080/07366299.2019.1646982

M3 - Journal article

VL - 37

SP - 376

EP - 391

JO - Solvent Extraction and Ion Exchange

JF - Solvent Extraction and Ion Exchange

SN - 0736-6299

IS - 5

ER -