Spinlab

Manufactured by GE Healthcare

Sourced in United States, Denmark

The SPINlab is a compact, bench-top nuclear magnetic resonance (NMR) spectrometer designed for analytical applications in the life sciences, chemical, and manufacturing industries. It provides a reliable and efficient solution for a range of sample analysis tasks, delivering high-quality data to support research and quality control efforts.

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Lab products found in correlation

Ah111501, by GE Healthcare (2 mentions) Gmp precursor, by Merck Group (2 mentions) Achieva 3t mri, by Philips (1 mentions) Ox063, by Oxford Instruments (1 mentions) Hypersense system, by Oxford Instruments (1 mentions) Gmp grade 14 m 1 13c pyruvic acid, by Merck Group (1 mentions) Vnmrj 4.0a, by Agilent Technologies (1 mentions) Mr750, by GE Healthcare (1 mentions) 1 13c pyruvic acid, by Merck Group (1 mentions) Trityl radical ox063, by Oxford Instruments (1 mentions) Dual tuned 13c 1h volume rat coil, by GE Healthcare (1 mentions) Biograph mmr, by Siemens (1 mentions)

21 protocols using spinlab

Hyperpolarized [1-13C]Pyruvate Injection

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Samples containing 1.47 g of Good Manufacturing Practice (GMP) grade [1-¹³C]pyruvate (MilliporeSigma Isotec) and 15 mM electron paramagnetic agent (EPA; AH111501, GE Healthcare) were prepared by a pharmacist the morning of the study. Samples were polarized using a 5T clinical polarizer (SPINlab, GE Healthcare) for at least two hours. Following dissolution, the electron paramagnetic agent was removed by filtration and pH, pyruvate and EPA concentrations, polarization, and temperature were measured prior to injection. In parallel, the integrity of the 0.5 μm sterile filter was tested in agreement with manufacturer specifications prior to injection. After release by the pharmacist, a 0.43 mL/kg dose of ~250 mM pyruvate was injected at a rate of 5 mL/s, followed by a 20 mL saline flush (0.9% sodium chloride, Baxter Healthcare Corporation), with the acquisition starting 5 s after the end of saline injection.

Gordon J.W., Chen H.Y., Autry A., Park I., Criekinge M.V., Mammoli D., Milshteyn E., Bok R., Xu D., Li Y., Aggarwal R., Chang S., Slater J.B., Ferrone M., Nelson S., Kurhanewicz J., Larson P.E, & Vigneron D.B. (2018). Translation of Carbon-13 EPI for Hyperpolarized MR Molecular Imaging of Prostate and Brain Cancer Patients. Magnetic resonance in medicine, 81(4), 2702-2709.

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Hyperpolarized [1-13C]Pyruvate Injection Protocol

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As described in the Online Data Supplement, all starting materials were prepared in a Grade A sterile environment^{23 (link)} before being loaded into a General Electric SpinLab system (GE Healthcare, Chicago) for the process of Dynamic Nuclear Polarization.^{12 (link)} Sufficient polarization levels were achieved after 2 to 3 hours, after which dissolution was undertaken to produce the final hyperpolarized [1-¹³C]pyruvate solution for injection. Solutions were only released for human injection if the following criteria were met: pH 6.7 to 8.4, temperature 25.0°C to 37.0°C, polarization ≥15%, (pyruvate) 220 to 280 mmol/L, (electron paramagnetic agent) ≤3.0 µmol/L, appearance: clear, colorless solution with no visible particulate matter. Administration of the hyperpolarized pyruvate was undertaken through an 18G venous cannula sited in the left antecubital fossa at a dose of 0.4 mL/kg and at a rate of 5 mL per second.

Rider O.J., Apps A., Miller J.J., Lau J.Y., Lewis A.J., Peterzan M.A., Dodd M.S., Lau A.Z., Trumper C., Gallagher F.A., Grist J.T., Brindle K.M., Neubauer S, & Tyler D.J. (2020). Noninvasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI. Circulation Research, 126(6), 725-736.

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Hyperpolarized 13C Metabolite Preparation

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Unless otherwise indicated, all chemicals and solvents were purchased from Sigma-Aldrich (St. Louis, MO). 13C metabolites were prepared for HP according to published reports: [1-13C] pyruvate24 (link), [1-13C] lactate35 (link), [13C,15N2] urea36 (link), [1-13C] dehydroascorbate and [1-13C] ascorbate21 (link). All metabolites were HP using a prototype SpinLab (General Electric, Niskayuna, New York, USA) for approximately 90 min before dissolving with appropriate buffers as described in previous publications.

Tee S.S., DiGialleonardo V., Eskandari R., Jeong S., Granlund K.L., Miloushev V., Poot A.J., Truong S., Alvarez J.A., Aldeborgh H.N, & Keshari K.R. (2016). Sampling Hyperpolarized Molecules Utilizing a 1 Tesla Permanent Magnetic Field. Scientific Reports, 6, 32846.

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Hyperpolarized Pyruvate Metabolism in Pig Model

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For sample preparation, 600 mg of [1‐¹³C] pyruvic acid was mixed with 15 mmol/L of a paramagnetic agent (EPA) as previously described in Ardenkjaer‐Larsen et al. (2011). In short, dissolution was performed with 29 mL of deionized water into a receiver syringe. The receiver syringe contained 13 mL of 360 mmol/L NaOH and 180 mmol/L tris (hydroxymethyl)aminomethane (TRIS) for neutralization of the pyruvic acid. Four identical samples of the mixture of 600 mg of [1‐¹³C] pyruvic acid/ 15 mmol/L EPA were polarized in a SpinLab (GE Healthcare) for more than two hours to ensure approximately 40% polarization.
Twenty‐eight milliliter of hyperpolarized pyruvate solution (250 mmol, pH 7.4, isotonic) were injected into the pig via the left femoral vein catheter (Laustsen et al. 2015) at time 0, 20, 40 and 60 min. Five minutes after the first injection of hyperpolarized pyruvate, a bolus of 1 g/kg glucose (glucose, 500 g/L; SAD, Copenhagen, Denmark) was injected into the right femoral vein catheter over approximately 20 sec.

Kjærgaard U., Laustsen C., Nørlinger T., Tougaard R.S., Mikkelsen E., Qi H., Bertelsen L.B., Jessen N, & Stødkilde‐Jørgensen H. (2018). Hyperpolarized [1‐13C] pyruvate as a possible diagnostic tool in liver disease. Physiological Reports, 6(23), e13943.

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Hyperpolarized [1-13C] Pyruvate Production

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[1‐¹³C] Pyruvic acid was mixed with AH111501 electron paramagnetic agent and loaded into a fluid path under aseptic conditions.
⁶ ,
¹¹ (link) The fluid path was irradiated with microwaves at <1 K for approximately 2 h in a clinical hyperpolarizer (SPINLab, GE Healthcare, Chicago, Il, USA). Polarization level (n = 8), measured by the SPINLab, at the point of dissolution: 27 ± 4 (mean ± 95% CI). The frozen sample was then dissolved with sterile heated water (38 mL) and neutralized with 17.5 g sterile trometamol buffer (333 mM Tris and 600 mM NaOH); >40 mL of hyperpolarized [1‐¹³C] pyruvate solution was produced at the following concentration: 251–270 mM, temperature: 35.6–39°C, and pH: 6.7–7.6. Injection of the hyperpolarized agent started 70–81 seconds after dissolution, with data acquisition beginning immediately after the completion of the injection. Exactly 40 mL of hyperpolarized [1‐¹³C] pyruvate was injected into each patient and followed by a saline flush (60 mL).

Chowdhury R., Mueller C.A., Smith L., Gong F., Papoutsaki M., Rogers H., Syer T., Singh S., Brembilla G., Retter A., Bullock M., Caselton L., Mathew M., Dineen E., Parry T., Hennig J., von Elverfeldt D., Schmidt A.B., Hövener J., Emberton M., Atkinson D., Bainbridge A., Gadian D.G, & Punwani S. (2022). Quantification of Prostate Cancer Metabolism Using 3D Multiecho bSSFP and Hyperpolarized [1‐13C] Pyruvate: Metabolism Differs Between Tumors of the Same Gleason Grade. Journal of Magnetic Resonance Imaging, 57(6), 1865-1875.

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In Vivo Hyperpolarized [1-^13C] NAC Imaging

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NaOH (5 M) was added to [1-¹³C] NAC powder and OX063 to produce a 3.2 M [1-¹³C] NAC solution with 17 mM OX063 at pH of 7.5. 35 mL of 3.2 M [1-¹³C] NAC with 17 mM OX063 was hyperpolarized using the SPINlab (GE Healthcare) for 3–4 h, and the scans were performed using the Philips Achieva 3 T MRI. ¹³C two dimensional spectroscopic chemical shift images (CSIs) were acquired with a 28 × 28 mm, field of view in a 10 mm axial slice through the head, a matrix size of 14 × 14, spectral width of 3333 Hz, repetition time of 86 ms, and excitation pulse width a flip angle of 3° for the mouse head, and with a 32 × 32 mm, field of view in a 10 mm coronal slice through the body, a matrix size of 16 × 16, spectral width of 3333 Hz, repetition time of 85 ms, and excitation pulse with a flip angle of 10° for the mouse body. CSIs were acquired 30 s after the beginning of the hyperpolarized [1-¹³C] NAC injections.

Yamamoto K., Opina A., Sail D., Blackman B., Saito K., Brender J.R., Malinowski R.M., Seki T., Oshima N., Crooks D.R., Kishimoto S., Saida Y., Otowa Y., Choyke P.L., Ardenkjær-Larsen J.H., Mitchell J.B., Linehan W.M., Swenson R.E, & Krishna M.C. (2021). Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine. Scientific Reports, 11, 12155.

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Dynamic Nuclear Polarization of [13C]-Glycerol

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The samples to be polarized consisted of a mixture of [¹³C]-Glyc in 3.0 M glycerol/water (3/2, v/v) solution containing 15 mM trityl radical OX063 (Oxford Instruments Molecular Biotools, Oxford, UK). The samples were polarized via dynamic nuclear polarization using either a SPINLab (General Electric, Niskayuna, New York, USA) or HyperSense system (Oxford Instruments Molecular Biotools, Oxford, UK). The polarized samples were dissolved in a solution of 40 mM Tris buffer, 50 mM NaCl, and 0.1 g/L EDTA-Na₂, leading to an 80 mM solution of the hyperpolarized substrate with a pH of approximately 7.5. The resulting buffered hyperpolarized [¹³C]-Glyc solution was used directly in T₁ measurements at 3 T.

Park J.M., Wu M., Datta K., Liu S.C., Castillo A., Lough H., Spielman D.M, & Billingsley K.L. (2017). Hyperpolarized Sodium [1-13C]-Glycerate as a Probe for Assessing Glycolysis In Vivo. Journal of the American Chemical Society, 139(19), 6629-6634.

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Dynamic Nuclear Polarization of Pyruvic Acid

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Four identical samples of 600 mg of [1‐¹³C]pyruvic acid mixed with 15mM AH111501 (trisodium salt of tris{8‐carboxyl‐2,2,6,6‐tetra[2‐(1‐methoxyethyl)]‐benzo(1,2‐d:4,5‐d')bis1, 3dithiole‐4‐yl}methyl acid was polarized in a SPINLab (GE Healthcare, Broendby, Denmark) polarizer 10 for more than 2.5 h at 5 Tesla (T) at 0.8 K, to ensure a reproducible polarization of 30% on average. Dissolution was performed with 20 mL of de‐ionized water into a receiver syringe, containing 16.3 mL of 360 mM sodium hydroxide (NaOH) and 180 mM tris(hydroxymethyl)aminomethane (TRIS) for neutralization of the pyruvic acid. Approximately 30 mL of 250 mM pyruvate concentration (20 mg/kg), similar to the dose administered in Nelson et al 3, was administered intravenously in 5 s in the femoral vein.

Laustsen C., Hansen E.S., Kjærgaard U., Bertelsen L.B., Ringgaard S, & Stødkilde‐Jørgensen H. (2015). Acute porcine renal metabolic effect of endogastric soft drink administration assessed with hyperpolarized [1‐13c]pyruvate. Magnetic Resonance in Medicine, 74(2), 558-563.

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Hyperpolarized [1-13C]Pyruvate Cellular Metabolism

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Research-grade fluid paths (RFP; GE Healthcare, Chicago, IL, USA) were filled with 35 mg of [1-¹³C]pyruvic acid doped with 15 mM electron paramagnetic agent (trityl radical AH111501; GE Healthcare, Chicago, IL, USA) and 14 g of water containing 0.1 g/L ethylenediaminetetraacetic acid (EDTA) dissolution medium. Samples were polarized using a clinical hyperpolarizer (SPINlab; GE Healthcare, Chicago, IL, USA) at a temperature of 0.8 K and a magnetic field of 5 T for an average of 180 min. Following rapid dissolution, the pyruvic acid solution was neutralized and diluted with TRIS-buffered NaOH solution to obtain approximately 5 mL of [1-¹³C]pyruvate solution at neutral pH. Next, 1 mL of the fluid containing approximately 75 mM hyperpolarized [1-¹³C]pyruvate was immediately added to 9 mL of the cell suspension in a syringe, resulting in a final pyruvate concentration range of 7.0–7.5 mM. The time intervals between the dissolution of hyperpolarized [1-¹³C]pyruvate and the start of ¹³C-MRI acquisition ranged from 62 to 77 s. The temperature of the samples was regulated at approximately 37.0 °C during MR imaging. The pH levels of the samples ranged from 5.9 to 6.4. The experiments were repeated three times for the non-irradiated and irradiated cells, including FaDu cancer cells, HMC3 microglial cells, and THP-1 monocytes.

Lai Y.C., Hsieh C.Y., Lu K.Y., Sung C.H., Ho H.Y., Cheng M.L., Chen A.P., Ng S.H., Chen F.H, & Lin G. (2021). Monitoring Early Glycolytic Flux Alterations Following Radiotherapy in Cancer and Immune Cells: Hyperpolarized Carbon-13 Magnetic Resonance Imaging Study. Metabolites, 11(8), 518.

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Hyperpolarized 13C Pyruvate Production

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A clinical SPINlab^™ polarizer (GE Healthcare) was used for DNP. Up to three pyruvate samples were simultaneously polarized for each subject. Each pyruvate sample was prepared by mixing 1.47 g of GMP-grade 14-M [1-¹³C]pyruvic acid (Sigma Aldrich, St Louis, Missouri, USA) with 27.7 mg of AH111501 EPA radical (Syncom, Groningen, Netherlands). After assembly in sterile environment, clinical fluid paths were transferred to the SPINlab for polarization and compounding. The pyruvate samples were polarized for 3 – 4.5 hrs, then dissolved by 38 mL of sterile water at 130 °C. The HP pyruvate solution was mixed with 36.5 mL of room temperature TRIS/NaOH media (333 mM/600 mM) and passed a quality control (QC) analysis prior to the injection. Terminal filtering, filter integrity bubble point test, pH strip confirmation and volume check were performed in addition to the automated QC. For each ¹³C acquisition, a bodyweight-adjusted volume (0.43 mL/kg) of 250 mM pyruvate was injected at a rate of 5 mL/s, followed by a 25-mL saline flush at the same rate. Pyruvate concentration (242.6 ± 16.2 mM, n = 7), pH (7.6 ± 0.4), polarization level (33.7 ± 6.0 %), and residual radical (0.9 ± 0.8 μM) of the injectate were measured using the QC device (GE Healthcare) immediately after each dissolution. The transfer time from dissolution to the beginning of injection was 63.1 ± 6.7 s.

Ma J., Pinho M.C., Harrison C.E., Chen J., Sun C., Hackett E.P., Liticker J., Ratnakar J., Reed G.D., Chen A.P., Sherry A.D., Malloy C.R., Wright S.M., Madden C.J, & Park J.M. (2021). Dynamic 13C MR spectroscopy as an alternative to imaging for assessing cerebral metabolism using hyperpolarized pyruvate in humans. Magnetic resonance in medicine, 87(3), 1136-1149.

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