Automated and efficient radiosynthesis of [18F]FLT using a low amount of precursor

Marchand, Patrice; Ouadi, Ali; Pellicioli, M.; Schuler, J.; Laquerrière, Patrice; Boisson, Fréderic; Brasse, David

doi:10.1016/j.nucmedbio.2016.05.009

Cited by 23 publications

(14 citation statements)

References 33 publications

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“…As described above for compound 21b, the azetidine moiety was then coupled on the C-8 position of the quinoline core of derivative 23 using freshly prepared azetidin-3-ol trifluoroacetate [36] to produce compound 24 with a yield of 51%. the ratio of nosylate precursor to base was also shown to be crucial for the labeling process [40,42]. In the presence of an excess amount of base, the precursor is undergoing an E2 elimination mechanism, thus reducing the desired nucleophilic 18 F-fluorination [42].…”

Section: Synthesis Of the Precursor Compoundsmentioning

confidence: 99%

Targeting cyclic nucleotide phosphodiesterase 5 (PDE5) in brain: Toward the development of a PET radioligand labeled with fluorine-18

Wenzel

Liu

Dukić-Stefanović

et al. 2019

Bioorganic Chemistry

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With the aim to develop a specific radioligand for imaging the cyclic nucleotide phosphodiesterase 5 (PDE5) in brain by positron emission tomography (PET), seven new fluorinated inhibitors (3-9) were synthesized on the basis of a quinoline core. The inhibitory activity for PDE5 together with a panel of other PDEs was determined in vitro and two derivatives were selected for IC50 value determination. The most promising compound 7 (IC50 = 5.92 nM for PDE5A), containing a 3-fluoroazetidine moiety, was further radiolabeled by aliphatic nucleophilic substitution of two different leaving groups (nosylate and tosylate) using [ 18 F]fluoride. The use of the nosylate precursor and tetra-n-butyl ammonium [ 18 F]fluoride ([ 18 F]TBAF) in 3-methyl-3-pentanol combined with the addition of a small amount of water proved to be the best radiolabeling conditions achieving a RCY of 4.9 ± 1.5% in an automated procedure. Preliminary biological investigations in vitro and in vivo were performed to characterize this new PDE5 radioligand. Metabolism studies of [ 18 F]7 in mice revealed a fast metabolic degradation with the formation of radiometabolites which have been detected in the brain.

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Section: Synthesis Of the Precursor Compoundsmentioning

confidence: 99%

Targeting cyclic nucleotide phosphodiesterase 5 (PDE5) in brain: Toward the development of a PET radioligand labeled with fluorine-18

Wenzel

Liu

Dukić-Stefanović

et al. 2019

Bioorganic Chemistry

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show abstract

“…The focus was on the design of better-suited labelling precursors with respect to protection and leaving group [94][95][96][97][98][99][100]. The best RCY was received, using 5'-O-(4,4'dimethoxytriphenylmethyl)-2,3'-anhydrothymidine (DMTThy) as labelling precursor [98,99,[101][102][103]].…”

Section: Progress In Aliphatic Nucleophilic 18 F-fluorinationmentioning

confidence: 99%

“…As an example, a plug-and-play radiosynthesis platform accompanied by computer software based on modular subunits can easily and flexibly be configured to implement a diverse range of radiosynthesis protocols [194]. Using such systems, the standard procedures ( 18 F-labelling, hydrolysis and purification) have been implemented for many clinically relevant 18 F-tracers [103,105,191,[195][196][197] or 18 Flabelled building blocks for labelling of macromolecules [198][199][200] and build-up syntheses [145].…”

Section: Automation Of Nucleophilic 18 F-fluorinationmentioning

confidence: 99%

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18F-labelling innovations and their potential for clinical application

Coenen

Neumaier

2018

Clin Transl Imaging

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An impressive variety of new methodologies for the preparation of 18 F-labelled tracers and ligands has appeared over the last decade. Most strategies of the newly developed radiofluorination methods predominantly aim at products of high molar activity by 'late-stage' labelling of small (hetero)aromatic molecules and the use of transition metals. This is accompanied by the improvement of technical procedures, like preparation of reactive [ 18 F]fluoride and automated syntheses. The newly introduced procedures reflect a high innovative level and creativity in radio(pharmaceutical) chemistry at present, which are based on modern chemical methods and deep mechanistic insights. Taking also automation and quality control into consideration, major recently developed radiofluorination methods, most of those still under development, are compiled here in view of their potential for clinical PET imaging and thus the ability to advance molecular imaging.

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“…Indeed, [ 18 F]FLT suitable for microPET studies has been efficiently synthesised from 15 using an electrowetting-ondielectric digital microfluidic chip [64] and an automated and efficient radiosynthesis of [ 18 F]FLT using a low amount of 15 (5 mg) has been developed, achieving a corrected radiochemical yield of 54% in a time of 52 minutes [65].…”

Section: F]flt Inside Cellsmentioning

confidence: 99%

Nucleoside transporters in PET imaging of proliferating cancer cells using 3ꞌ-deoxy-3ꞌ-[18F]fluoro-L-thymidine

Saidijam¹,

Afshar²,

Ahmad³

et al. 2018

J Diagn Imaging Ther

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The movement of physiologic nucleosides and nucleoside analogue drugs across biological membranes is mediated by nucleoside transport proteins. In cancer, nucleoside transporters have an important role in maintaining the hyperproliferative state of tumours and are important targets for diagnostic and therapeutic agents in the detection, treatment and monitoring of cancers. The nucleoside-based probe 3ꞌ-deoxy-3ꞌ-

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Automated and efficient radiosynthesis of [18F]FLT using a low amount of precursor

Cited by 23 publications

References 33 publications

Targeting cyclic nucleotide phosphodiesterase 5 (PDE5) in brain: Toward the development of a PET radioligand labeled with fluorine-18

Targeting cyclic nucleotide phosphodiesterase 5 (PDE5) in brain: Toward the development of a PET radioligand labeled with fluorine-18

18F-labelling innovations and their potential for clinical application

Nucleoside transporters in PET imaging of proliferating cancer cells using 3ꞌ-deoxy-3ꞌ-[18F]fluoro-L-thymidine

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