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Research ArticleRADIOPHARMACY

Fully Automated Production of Diverse 18F-Labeled PET Tracers on the ELIXYS Multireactor Radiosynthesizer Without Hardware Modification

Mark Lazari, Jeffrey Collins, Bin Shen, Mohammed Farhoud, Daniel Yeh, Brandon Maraglia, Frederick T. Chin, David A. Nathanson, Melissa Moore and R. Michael van Dam
Journal of Nuclear Medicine Technology September 2014, 42 (3) 203-210; DOI: https://doi.org/10.2967/jnmt.114.140392
Mark Lazari
1Department of Bioengineering, Henry Samueli School of Engineering, UCLA, Los Angeles, California
2Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
3Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California
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Jeffrey Collins
2Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
3Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California
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Bin Shen
4Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Stanford, California
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Mohammed Farhoud
5Sofie Biosciences, Inc., Culver City, California; and
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Daniel Yeh
2Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
6Ahmanson Translational Imaging Division, David Geffen School of Medicine, UCLA, Los Angeles, California
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Brandon Maraglia
2Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
3Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California
5Sofie Biosciences, Inc., Culver City, California; and
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Frederick T. Chin
4Molecular Imaging Program at Stanford (MIPS) Department of Radiology, Stanford University, Stanford, California
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David A. Nathanson
2Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
6Ahmanson Translational Imaging Division, David Geffen School of Medicine, UCLA, Los Angeles, California
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Melissa Moore
2Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
3Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California
5Sofie Biosciences, Inc., Culver City, California; and
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R. Michael van Dam
1Department of Bioengineering, Henry Samueli School of Engineering, UCLA, Los Angeles, California
2Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
3Crump Institute for Molecular Imaging, David Geffen School of Medicine, UCLA, Los Angeles, California
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  • FIGURE 1.
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    FIGURE 1.

    Disposable cassette fluidic paths used for 3-reactor syntheses. (A) Top view with fluidic connections inside (dashed) and outside (solid) each cassette, including purification cartridges. Side view of cassettes display reactor in Add position (B), where fluid is delivered into reaction vessel, and Transfer position (C), where fluid is transferred out of reaction vessel. SPE = solid phase extraction; QMA = quarternary methylammonium.

  • FIGURE 2.
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    FIGURE 2.

    Examples of HPLC chromatograms. (A and B) 18F-FLT semipreparative HPLC (A) and analytic HPLC of purified sample with coinjection of standard (B). (C and D) 18F-FHBG semipreparative HPLC (C) and analytic HPLC of purified sample with coinjection of standard (D). Chromatography conditions are found in Supplemental Table 2. *Radioactive peak of interest. AU = absorbance units; CPS = counts per second; UV = ultraviolet.

  • FIGURE 3.
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    FIGURE 3.

    Small-animal PET imaging using same-day sequentially synthesized PET tracers on single automated radiosynthesizer. Sample images are shown for 18F-FLT (A), 18F-FDG (B), and 18F-fallypride (C). Scale for percentage injected dose per gram (%ID/g) is listed for each image. BL = bladder; BM = bone marrow; GB = gallbladder; GI = gastrointestinal tract; HR = heart; KD = kidneys; LG = lacrimal glands; ST = striatum; TM = A431 implanted tumor.

  • FIGURE 4.
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    FIGURE 4.

    Chromatograms of purified and reformulated products. (A) d-18F-FAC analytic HPLC with coinjection of standard. (B) 18F-FDG radio-TLC. Chromatography conditions are found in Supplemental Table 2. AU = absorbance units; CPS = counts per second; UV = ultraviolet.

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    TABLE 1

    Summary of Synthesis Data

    Specific activity†
    TracerDecay-corrected radiochemical yield (%)Synthesis duration (min)*GBq/μmolCi/μmol
    d-18F-FAC31 ± 4 (n = 11)16337–441.0–1.2
    l-18F-FMAU49 ± 7 (n = 7)170100–1702.7–4.6
    d-18F-FEAU (3-reactor)39 ± 4 (n = 3)1803.8–5.1‡0.10–0.14
    d-18F-FEAU (1-reactor)28 ± 4 (n = 3)1407.4–20‡0.20–0.53
    18F-FDG70 ± 9 (n = 3)38NA
    18F-FLT69 ± 3 (n = 5)6567–4811.8–13
    18F-fallypride66 ± 8 (n = 6)5615–78‡0.4–2.1
    18F-FHBG11 ± 2 (n = 3)8792–1892.5–5.1
    18F-SFB69 ± 8 (n = 6)78631.7
    • ↵* Synthesis duration was defined from start of synthesis to end of synthesis, including purification but not including reformulation.

    • ↵† Range of specific activities measured at time of injection into analytic HPLC.

    • ↵‡ Starting activity was lower than average and ranged from 1.3 to 1.9 GBq (35–50 mCi).

    • NA = not applicable.

    • Radiochemical yields are mean ± SD.

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Journal of Nuclear Medicine Technology: 42 (3)
Journal of Nuclear Medicine Technology
Vol. 42, Issue 3
September 1, 2014
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Fully Automated Production of Diverse 18F-Labeled PET Tracers on the ELIXYS Multireactor Radiosynthesizer Without Hardware Modification
Mark Lazari, Jeffrey Collins, Bin Shen, Mohammed Farhoud, Daniel Yeh, Brandon Maraglia, Frederick T. Chin, David A. Nathanson, Melissa Moore, R. Michael van Dam
Journal of Nuclear Medicine Technology Sep 2014, 42 (3) 203-210; DOI: 10.2967/jnmt.114.140392

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Fully Automated Production of Diverse 18F-Labeled PET Tracers on the ELIXYS Multireactor Radiosynthesizer Without Hardware Modification
Mark Lazari, Jeffrey Collins, Bin Shen, Mohammed Farhoud, Daniel Yeh, Brandon Maraglia, Frederick T. Chin, David A. Nathanson, Melissa Moore, R. Michael van Dam
Journal of Nuclear Medicine Technology Sep 2014, 42 (3) 203-210; DOI: 10.2967/jnmt.114.140392
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Keywords

  • automated radiosynthesis
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  • 18F-FAC
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  • 18F-FMAU
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