Fully automated one-pot radiosynthesis of O-(2-[18F]fluoroethyl)-l-tyrosine on the TracerLab FXFN module

Bourdier, Thomas; Greguric, Ivan; Roselt, Peter; Jackson, Tim; Faragalla, Jane; Katsifis, Andrew

doi:10.1016/j.nucmedbio.2011.01.001

Cited by 35 publications

(23 citation statements)

References 11 publications

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“…18 F-FDG was synthesized using GE FASTlab methodology according to the manufacturer‘s instructions. 18 F-FET was synthesized on a GE TRACERlab FX-FN as previously described by Bourdier et al [13]. 11 C-MET was synthesized on a GE TRACERlab FX-C Pro by on-column 11 C-methylation of L -homocysteine with 11 CH 3 I according to the procedures described by Kniess [14] and Gomzina and co-workers [15].…”

Section: Methodsmentioning

confidence: 99%

Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology

Lückerath¹,

Lapa²,

Spahmann³

et al. 2013

PLoS ONE

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PurposeMultiple myeloma is a hematologic malignancy originating from clonal plasma cells. Despite effective therapies, outcomes are highly variable suggesting marked disease heterogeneity. The role of functional imaging for therapeutic management of myeloma, such as positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG-PET), remains to be determined. Although some studies already suggested a prognostic value of 18F-FDG-PET, more specific tracers addressing hallmarks of myeloma biology, e.g. paraprotein biosynthesis, are needed. This study evaluated the amino acid tracers L-methyl-[11C]-methionine (11C-MET) and [18F]-fluoroethyl-L-tyrosine (18F-Fet) for their potential to image myeloma and to characterize tumor heterogeneity. Experimental DesignTo study the utility of 11C-MET, 18F-Fet and 18F-FDG for myeloma imaging, time activity curves were compared in various human myeloma cell lines (INA-6, MM1.S, OPM-2) and correlated to cell-biological characteristics, such as marker gene expression and immunoglobulin levels. Likewise, patient-derived CD138+ plasma cells were characterized regarding uptake and biomedical features.ResultsUsing myeloma cell lines and patient-derived CD138+ plasma cells, we found that the relative uptake of 11C-MET exceeds that of 18F-FDG 1.5- to 5-fold and that of 18F-Fet 7- to 20-fold. Importantly, 11C-MET uptake significantly differed between cell types associated with worse prognosis (e.g. t(4;14) in OPM-2 cells) and indolent ones and correlated with intracellular immunoglobulin light chain and cell surface CD138 and CXCR4 levels. Direct comparison of radiotracer uptake in primary samples further validated the superiority of 11C-MET.ConclusionThese data suggest that 11C-MET might be a versatile biomarker for myeloma superior to routine functional imaging with 18F-FDG regarding diagnosis, risk stratification, prognosis and discrimination of tumor subtypes.

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Section: Methodsmentioning

confidence: 99%

Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology

Lückerath¹,

Lapa²,

Spahmann³

et al. 2013

PLoS ONE

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“…The microscale synthesis was adapted from previously described macroscale protocols (Bourdier et al 2011;Hamacher and Coenen 2002) by scaling down reagent volumes (Fig. 2).…”

Section: Microscale Radiosynthesis and Purification Of [ 18 F]fetmentioning

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%

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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“…Therefore, several attempts were made to improve the synthesis of [ 18 F]FET ( 22 ), especially with regards to its easier automation. Besides optimization of the two step procedure, a one‐pot procedure via an aliphatic substitution reaction of a protected tyrosine derivative bearing an O ‐ethyl moiety with a leaving group was developed and optimized . Alternatively, a novel type of enantiomerically pure labelling precursor, on the basis of a Ni(II) complex of a Schiff's base, was used for a nucleophilic build‐up reaction of this tracer …”

Section: F‐labelled Amino Acidsmentioning

confidence: 99%

Methods for ¹¹C‐ and ¹⁸F‐labelling of amino acids and derivatives for positron emission tomography imaging

Neumaier

Coenen

2013

Labelled Comp Radiopharmac

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The different concepts realized for the synthesis of (11) C- and (18) F-labelled amino acids are summarized. Carbon-11 enables principally authentic radiolabelling of natural occurring amino acids by substituting one of the skeleton carbons by the radionuclide. Fluorine-18 is a foreign element for natural amino acids. Because of its advantageous nuclidic properties for positron emission tomography, however, it becomes increasingly important in molecular imaging, also with amino acid analogues. Especially in the last decade, considerable progress has been made with the radiosynthesis of (18) F-labelled amino acids that are now clinically approved, and thus assure their availability. In contrast, the synthetic possibilities with (11) C-labelled amino acids are more limited because of the short half-life of carbon-11 which also hampers their wide spread use.

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Fully automated one-pot radiosynthesis of O-(2-[18F]fluoroethyl)-l-tyrosine on the TracerLab FXFN module

Cited by 35 publications

References 11 publications

Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology

Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology

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

Methods for ¹¹C‐ and ¹⁸F‐labelling of amino acids and derivatives for positron emission tomography imaging

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Fully automated one-pot radiosynthesis of O-(2-[18F]fluoroethyl)-l-tyrosine on the TracerLab FXFN module

Cited by 35 publications

References 11 publications

Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology

Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology

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

Methods for 11C‐ and 18F‐labelling of amino acids and derivatives for positron emission tomography imaging

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Methods for ¹¹C‐ and ¹⁸F‐labelling of amino acids and derivatives for positron emission tomography imaging