Fully automated synthesis of O-(2′-[18F]fluoroethyl)-l-tyrosine ([18F]FET) using solid phase extraction (SPE) purification with neutral alumina

Lakshminarayanan, Nandita; Kumar, Amit; Roy, S. K.; Pawar, Yogita; Chaudhari, Pradip; Rajan, M. G. R.

doi:10.1007/s10967-016-4900-8

Cited by 7 publications

(5 citation statements)

References 14 publications

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“…One significant change we made was altering the fluorination reaction solvent. The syntheses reported by Hamacher and Coenen (2002), Bourdier et al (2011) and Lakshminarayanan et al (2016) all used MeCN as the fluorination solvent, but in the droplet format, we found that the MeCN evaporated very quickly, resulting in poor yields. After exploring several solvent combinations that have been previously reported in droplet reactions (Keng and van Dam 2015), a 1:1 v/v mixture of MeCN and thexyl alcohol was selected.…”

Section: Microscale [ 18 F]fet Synthesis Optimization and Automationmentioning

confidence: 76%

“…Synthesis performed with 60 nmol precursor and 110 nmol TBAHCO 3 at 90°C for 5 min Lisova et al EJNMMI Radiopharmacy and Chemistry (2020) 5:1 evaporation of TFA and low deprotection efficiency. We then explored the use of HCl, as reported by Bourdier et al (2011) and Lakshminarayanan et al (2016). Using a deprotection reagent volume of 10 μL heated for 3 min at 90°C, we explored the effect of different HCl concentrations (Fig.…”

Section: Microscale [ 18 F]fet Synthesis Optimization and Automationmentioning

confidence: 99%

“…The radiosynthesis of [ 18 F]FET from the commercially available precursor (2S)-O-(2′-tosyloxyethyl)-N-trityl-tyrosine-tert-butyl ester (TET) consists of a radiofluorination step followed by a hydrolysis step. The conventional synthesis typically results in good radiochemical yields (RCYs), ranging from 19 to 64% (Bourdier et al 2011;Bouvet et al 2012;Hamacher and Coenen 2002;Iwata et al 2018;Lakshminarayanan et al 2016). Some efforts have been made to carry out the synthesis in microfluidic format.…”

Section: Introductionmentioning

confidence: 99%

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Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)

Lisova

Chen

Wang

et al. 2019

EJNMMI radiopharm. chem.

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Background: Conventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources. Using O-(2-[ 18 F]fluoroethyl)-Ltyrosine ([ 18 F]FET), we demonstrate that simple microvolume radiosynthesis techniques can improve the efficiency of production by consuming tiny amounts of precursor, and maintaining high molar activity of the tracers even with low starting activity. Procedures: The synthesis was carried out in microvolume droplets manipulated on a disposable patterned silicon "chip" affixed to a heater. A droplet of [ 18 F]fluoride containing TBAHCO 3 was first deposited onto a chip and dried at 100°C. Subsequently, a droplet containing 60 nmol of precursor was added to the chip and the fluorination reaction was performed at 90°C for 5 min. Removal of protecting groups was accomplished with a droplet of HCl heated at 90°C for 3 min. Finally, the crude product was collected in a methanol-water mixture, purified via analytical-scale radio-HPLC and formulated in saline. As a demonstration, using [ 18 F]FET produced on the chip, we prepared aliquots with different molar activities to explore the impact on preclinical PET imaging of tumor-bearing mice. Results: The microdroplet synthesis exhibited an overall decay-corrected radiochemical yield of 55 ± 7% (n = 4) after purification and formulation. When automated, the synthesis could be completed in 35 min. Starting with < 370 MBq of activity,~150 MBq of [ 18 F]FET could be produced, sufficient for multiple in vivo experiments, with high molar activities (48-119 GBq/μmol). The demonstration imaging study revealed the uptake of [ 18 F]FET in subcutaneous tumors, but no significant differences in tumor uptake as a result of molar activity differences (ranging 0.37-48 GBq/μmol) were observed. Conclusions: A microdroplet synthesis of [ 18 F]FET was developed demonstrating low reagent consumption, high yield, and high molar activity. The approach can be expanded to tracers other than [ 18 F]FET, and adapted to produce higher quantities of the tracer sufficient for clinical PET imaging.

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Section: Microscale [ 18 F]fet Synthesis Optimization and Automationmentioning

confidence: 76%

Section: Microscale [ 18 F]fet Synthesis Optimization and Automationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)

Lisova

Chen

Wang

et al. 2019

EJNMMI radiopharm. chem.

View full text Add to dashboard Cite

show abstract

“…The radiochemical yield was 54%–65%, and radiochemical purities were greater than 99% within 36 min 15 . Lakshminarayanan et al have synthesized [ 18 F]FET using 8 mg of the TET precursor and varied the amount of eluent (buffered saline) to 35 and 17 mL, resulting in a yield of 19.07 ± 1.3 and 8.76 ± 0.46%, respectively 16 . [ 18 F]FET is an established tracer for tumor imaging, and therefore, more of the studies are focused on decreasing the precursor quantity and increasing the yield.…”

Section: Introductionmentioning

confidence: 99%

Development of an economical method to synthesize O‐(2‐[¹⁸F]fluoroethyl)‐L‐tyrosine (¹⁸FFET)

Kumar

Joshi

Thakur

et al. 2023

Labelled Comp Radiopharmac

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Positron emission tomography (PET) using O‐(2‐[18F]fluoroethyl)‐L‐tyrosine ([18F]FET) has shown great success in differentiating tumor recurrence from necrosis. In this study, we are reporting the experience of synthesis [18F]FET by varying the concentration of TET precursor in different chemistry modules. TET precursor (2–10 mg) was used for the synthesis of [18F]FET in an automated (MX Tracerlab) module (n = 6) and semiautomated (FX2N Tracerlab) module (n = 19). The quality control was performed for all the preparations. For human imaging, 220 ± 50 MBq of [18F]FET was briefly injected into the patient to acquire PET‐MR images. The radiochemical purity was greater than 95% for the final product in both modules. The decay corrected average yield was 10.7 ± 4.7% (10 mg, n = 3) and 8.2 ± 2.6% (2 mg, n = 3) with automated chemistry module and 36.7 ± 7.3% (8–10 mg, n = 12), 26.4 ± 3.1% (5–7 mg, n = 4), and 35.1 ± 3.8% (2–4 mg, n = 3) with semiautomated chemistry modules. The PET imaging showed uptake at the lesion site (SUVmax = 7.5 ± 2.6) and concordance with the MR image. The [18F]FET was produced with a higher radiochemical yield with 2.0 mg of the precursor with substantial yield and is suitable for brain tumor imaging.

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“…The core of SPE is the adsorbent that determines the selectivity and sensitivity of the method. However, the widely used commercial SPE adsorbents, such as bonded silicas (C 8 , C 18 ), Graphene , Alumina N , and nanomaterials are often limited by their shortcomings, such as the high costs, potential health, and environmental risks and the narrow applicable ranges. Thus, developing new SPE adsorbents is of high value.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a mixed anionic–nonionic surfactant modified eggshell membrane as an advantageous adsorbent for the solid‐phase extraction of Sudan I–IV as model analytes

Liu

Wang

Bai

et al. 2017

J of Separation Science

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The coadsorption of mixed anionic-nonionic surfactants, sodium dodecylbenzenesulfonate with Triton X-100, on the surface of eggshell membrane was investigated based on adsorption isotherms to improve the solid-phase extraction performance of eggshell membrane toward organic contaminants. Results showed that even though excess Triton X-100 might inhibit the adsorption of sodium dodecylbenzenesulfonate, a low dosage of Triton X-100 can significantly improve sodium dodecylbenzenesulfonate modification and enhance the extraction efficiency of eggshell membrane from 73.7 to 100.4% because of the formation of mixed hemimicelles. The highest recovery was achieved at 2:8 (Triton X-100/sodium dodecylbenzenesulfonate mass ratios), and multiple mechanisms involving π-π interactions, hydrophobic effect, and π-π electron donor-acceptor interactions contributed to the strong extraction affinity. When mixed, the Triton X-100 and sodium dodecylbenzenesulfonate modified eggshell membrane packed cartridge coupled with high-performance liquid chromatography was applied for the simultaneous determination of trace Sudan I-IV, and low detection limits (0.16-0.26 ng/L) were achieved with satisfactory linearity (R > 0.999) in 10-10 000 μg/L. For real samples, Sudan II and III in one chilli sauce sample were found at 4.3 and 1.7 μg/kg. Sudan I-IV recoveries at three spiked levels were 87.4-102.9% with precisions <6.8%. Comparison with commonly used solid-phase extraction adsorbents and methods further reflected the superiorities of the proposed adsorbent in sensitivity, retention ability, and applicability.

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Fully automated synthesis of O-(2′-[18F]fluoroethyl)-l-tyrosine ([18F]FET) using solid phase extraction (SPE) purification with neutral alumina

Cited by 7 publications

References 14 publications

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)

Development of an economical method to synthesize O‐(2‐[¹⁸F]fluoroethyl)‐L‐tyrosine (¹⁸FFET)

Evaluation of a mixed anionic–nonionic surfactant modified eggshell membrane as an advantageous adsorbent for the solid‐phase extraction of Sudan I–IV as model analytes

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Fully automated synthesis of O-(2′-[18F]fluoroethyl)-l-tyrosine ([18F]FET) using solid phase extraction (SPE) purification with neutral alumina

Cited by 7 publications

References 14 publications

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)

Development of an economical method to synthesize O‐(2‐[18F]fluoroethyl)‐L‐tyrosine (18FFET)

Evaluation of a mixed anionic–nonionic surfactant modified eggshell membrane as an advantageous adsorbent for the solid‐phase extraction of Sudan I–IV as model analytes

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Development of an economical method to synthesize O‐(2‐[¹⁸F]fluoroethyl)‐L‐tyrosine (¹⁸FFET)