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

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    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.
    Original languageEnglish
    JournalSolvent Extraction and Ion Exchange
    Volume37
    Issue number5
    Pages (from-to)376-391
    ISSN0736-6299
    DOIs
    Publication statusPublished - 2019

    Keywords

    • Gallium-68
    • Gallium-67
    • Liquid extraction in flow
    • COSMO-RS

    Cite this

    @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",

    }

    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 -