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Qma cartridge

Manufactured by Waters Corporation
Sourced in Brazil, Germany, Japan

The QMA cartridge is a solid-phase extraction (SPE) device used for sample preparation in analytical chemistry. It is designed to selectively retain and concentrate analytes of interest from complex matrices prior to instrumental analysis. The QMA cartridge utilizes a quaternary methylamine sorbent for the purification and enrichment of anionic species. Its core function is to facilitate the efficient extraction and cleanup of these anionic compounds from various sample types.

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8 protocols using qma cartridge

1

Radiosynthesis of [18F]Flurpiridaz

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Example 1

[18F]-fluoride (ca. 100 GBq) was produced using a GE Medical Systems PETtrace cyclotron with a silver target via the [18O](p,n) [18F] nuclear reaction. Total target volumes of 3.2-4.8 mL were used. The radiofluoride was trapped on a Waters QMA cartridge (pre-conditioned with carbonate), and the fluoride was eluted with a solution of tetrabutylammnonium hydrogen carbonate (22 mg) in water (100 μL) and acetonitrile (400 μL). Nitrogen was used to drive the solution off the QMA cartridge to the reaction vessel. The [18F]fluoride was dried for 9 minutes at 120° C. under a steady stream of nitrogen and vacuum. The precursor (10.2 mg, synthesized according to known methods) in MeCN (1.7 mL) was added to the dried [18F]-fluoride and the reaction mixture was heated at 120° C. for 10 minutes. The crude product was diluted with water (9.3 mL) and analysed by HPLC.

The % of [18F]Flurpiridaz in the crude product was 81% with 13% of a late eluting radiolysis product (FIG. 1). In once instance of the radiosynthesis the inventors observed only 72% [18F]Flurpiridaz.

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2

Radiolabeling and Purification of [18F]6

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Fluorine-18, trapped on a QMA cartridge (Waters Corp, Milford, MA), was obtained from PETNET Solutions (Durham, NC). The 18F activity was eluted from the cartridge using tetraethylammonium bicarbonate (3 mg/mL) in acetonitrile and water (80/20, v/v, 1 mL). Solvents were evaporated at 100°C and the residual water was removed by azeotroping with acetonitrile (3 × 0.3 mL) at 100°C. Trimethylammonium triflate precursor 11 (0.3 mg, 0.27 μmol) in 0.15 mL anhydrous acetonitrile was added to the dried 18F activity (2.0–3.1 GBq; 53.6–83.2 mCi), and the mixture was heated at 40°C for 15 min. The crude mixture containing [18F]6 was purified using the Beckman Gold HPLC system using an XBridge C18 column eluted with 53% ethanol in sodium acetate buffer (0.05 M, pH 5.5) at a flow rate of 1.5 mL/min (tR of [18F]6 = 16.4 min). For in vitro cell studies, [18F]6 isolated from the HPLC was added directly to the cell culture medium with the result that the ethanol concentration in the medium was <0.2%. For in vivo studies in mice, HPLC-purified [18F]6 was diluted with PBS to adjust the ethanol concentration to ≤10% before injection. For assessing the molar activity (Am) of [18F]6, the [18F]6 peak was concentrated using an Oasis® Light HLB cartridge (30 mg sorbent, Waters).
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3

Radiolabeling of [18F]Flurpiridaz with TEMPO

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Example 2

[18F]-fluoride (ca. 100 GBq) was produced using a GE Medical Systems PETtrace cyclotron with a silver target via the [18O](p,n) [18F] nuclear reaction. Total target volumes of 3.2-4.8 mL were used. The radiofluoride was trapped on a Waters QMA cartridge (pre-conditioned with carbonate), and the fluoride was eluted with a solution of tetrabutylammnonium hydrogen carbonate (22 mg) in water (100 μL) and acetonitrile (400 μL). Nitrogen was used to drive the solution off the QMA cartridge to the reaction vessel. The [18F]-fluoride was dried for 9 minutes at 120° C. under a steady stream of nitrogen and vacuum. A mixture of the precursor (10.2 mg) and TEMPO (1.7 mg) in MeCN (1.7 mL) was added to the dried [18F]-fluoride and the reaction mixture was heated at 120 C for 10 minutes. The crude product was diluted with water (9.3 mL) and analysed by HPLC.

The % of [18F]Flurpiridaz in the crude product was 92% with 1% of the late eluting radiolysis product. The addition of TEMPO to the labelling reaction reduces the amount of the late eluting radiolysis product (FIG. 1). The present inventors deduce from these results that even when carried out at high activity the addition of TEMPO to the radiolabelling reaction acts to reduce the late eluting radiolysis product.

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4

Radiolabeling of [18F]Fluoride via Solid-Phase Extraction

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The irradiated water containing the [18F]F was loaded onto a pre-conditioned QMA cartridge (Waters, Brazil) (130 mg, quaternary ammonium, carbonate form), and [18F]F was eluted off with 1 mL of K2CO3 (2 mg, 14 µmol)/Kryptofix 2.2.2 (K222, 11 mg, 29 µmol) mixture in 2:8 Milli-Q water/MeCN [29 (link)]. [K+/K222]/[18F]F/CO32− complex was dried by azeotropic distillation at 100 °C and nitrogen atmosphere with sequential addition of MeCN (1 mL, 3 times).
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5

Automated Radiosynthesis of [18F]LU14

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Remote-controlled radiosynthesis was performed using a Synchrom R&D EVO III automated synthesiser (Elysia-Raytest, Straubenhardt, Germany). Briefly, [18F]fluoride (4–6 GBq) was trapped on a Waters QMA cartridge and eluted with a solution containing 5.6 mg K222 and 40 μL K2CO3 dissolved in a mixture of H2O/MeCN (1 mL, 1:4, v/v) into the reaction vessel and dried via azeotropic distillation. An additional 1.5 mL of dried MeCN was added. After complete dryness, a solution containing 1 mg of precursor 7 in 800 µL DMSO was added, and the reaction mixture was stirred at 150 °C for 10 min. Upon cooling to 40 °C, the reaction mixture was diluted with 4 mL H2O, and the resulting solution was transferred to the semi-preparative HPLC. [18F]LU14 was collected in the HPLC collection vial containing 40 mL of H2O and trapped in the Sep-Pak® C18 light cartridge (Waters GmbH, Eschborn, Germany). The cartridge was washed with 2 mL H2O, and [18F]LU14 was eluted with 1.2 mL EtOH. This ethanolic solution was transferred outside of the shielded cell, and the solvent was evaporated at 70 °C in a gentle stream of nitrogen for 5–10 min, and [18F]LU14 was reconstituted in isotonic saline solution for further biological characterisation. Total synthesis time was about 70 min.
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6

Remote-Controlled Radiosynthesis of [18F]LUZ5-d8

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Remote-controlled radiosynthesis
was performed using a Synchrom R&D EVO III automated synthesizer
(Elysia-Raytest). Briefly, [18F]fluoride (5–12 GBq)
was trapped on a Waters QMA cartridge, eluted with a H2O/CH3CN [1 mL, 1:4 (v/v)] solution containing 2.2.2-cryptand
(K2.2.2) (11 mg) and K2CO3 (75 μL)
into the reaction vessel, and dried via azeotropic distillation. To
complete the azeotropic distillation, additional dry CH3CN (1.5 mL) was added. After complete dryness, precursor 19 (1 mg, 22.65 μmol) in CH3CN (1 mL) was added and
the reaction mixture was stirred at 90 °C for 10 min. The reaction
mixture was diluted with 4 mL of H2O/CH3CN (1:1),
and the solution was transferred to the semipreparative HPLC instrument. [18F]LUZ5-d8 was collected via the HPLC collection
vial containing 40 mL of H2O and trapped in the Sep-Pak
C18 light cartridge. The cartridge was washed with 2 mL of H2O, and [18F]LUZ5-d8 was eluted with 1.3 mL
of EtOH. This ethanolic solution was transferred outside of the shielded
cell; the solvent was evaporated at 70 °C in a gentle stream
of nitrogen for 5–10 min, and [18F]LUZ5-d8 was reconstituted in an isotonic saline solution for further biological
characterization. The total synthesis time was ∼85 min.
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7

Automated Radiosynthesis of [18F]RM365

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Remote
controlled radiosynthesis was performed using a Synchrom R&D EVO
III automated synthesizer (Elysia-Raytest, Straubenhardt, Germany).
Briefly, [18F]fluoride (8–12 GBq) was trapped on
a Waters QMA cartridge and eluted with a solution containing 100 μL
of TBAHCO3 and 30 μL of K2CO3 dissolved in a mixture of H2O/MeCN (1 mL, 1:4, v/v) into the reaction vessel and dried via azeotropic distillation.
A further 1.5 mL of dried MeCN was added. After complete dryness,
a solution of 13.2 μmol of Cu(Py)4(OTf)2 in 450 μL of DMA/t-BuOH (2:1, v/v) was added, followed by a solution of 6.6 μmol of boronic
acid pinacol ester 24 in 450 μL of DMA/t-BuOH (2:1, v/v), and the reaction mixture
was stirred at 120 °C for 10 min. Upon cooling to 40 °C,
the reaction mixture was diluted with H2O/MeCN (4 mL, 1:4, v/v), and the solution was transferred to the semipreparative
HPLC. [18F]RM365 was collected in the HPLC collection vial
containing 40 mL of H2O and trapped in the Sep-Pak C18
light cartridge. The cartridge was washed with 2 mL of H2O and [18F]RM365 eluted with 1.3 mL of EtOH. This ethanolic
solution was transferred outside of the shielded cell, the solvent
was evaporated at 70 °C in a gentle stream of nitrogen for 5–10
min, and [18F]RM365 was reconstituted in an isotonic saline
solution for further biological characterization. The total synthesis
time was about 75 min.
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8

Radiolabeling of Al^18F-NOTA-FAPI

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As shown in Fig. 1, radiolabeling of Al 18 F-NOTA-FAPI was completed based on a previous reported method with some modifications [20] . Briefly, 18 F  was produced from HM-20 medical cyclotron (Sumitomo Corporation, Japan), loaded on QMA cartridge (Waters Corporation, USA) and further eluted with saline (0.3-0.5 mL). For the radiolabeling, 18 F  in saline (0.1 mL, 555-3330 MBq) was mixed with AlCl3 (6 μL, 2 mM) and KHP (6 μL, 0.5 M) for 5 min under room temperature to form the [Al 18 F] 2+ conjugate, NOTA-FAPI precursor (5 μL, 4 mM) was further added to the reaction system and heated at 110 o C for 15 min. After that, the reaction system was diluted with 5 mL of ultrapure water and purified with Sep-Pak Light C18 cartridge (Waters Corporation, USA). Final product was formulated through the elution of C18 cartridge with 0.5 mL of 80% ethanol and 6 mL of saline consecutively, and further passed through a 0.2 μm syringe filter (Pall Corpotation, USA). The radiochemical purity of Al 18 F-NOTA-FAPI was analyzed by a radio high performance liquid chromatograph (1200 Series, Agilent, USA) with gradient elution: 0-3 min, 95% water (0.1% TFA) + 5% acetonitrile (0.1% TFA); 18 min, 5% water (0.1% TFA) + 95% acetonitrile (0.1% TFA); 20 min, 95% water (0.1% TFA) + 5% acetonitrile (0.1% TFA).
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