Nucleophilic 18F-Fluorination of Complex Molecules in Activated Carbocyclic Aromatic Position

Ermert, Johannes; Coenen, Heinz H.

doi:10.2174/1874471011003020109

Cited by 13 publications

(9 citation statements)

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“…Although direct labeling is the method of choice with short-lived radionuclides and build-up syntheses are normally reserved for cases when the former failed, 27,28 in direct comparison of both methods here, the latter led to better results. In both cases of direct labeling of 9b and 7e, only RCYs of about 1-5% were achieved at the end of synthesis (cf.…”

Section: Comparison Of Methodsmentioning

confidence: 99%

Labeling of benzodioxin piperazines with fluorine‐18 as prospective radioligands for selective imaging of dopamine D₄ receptors

Kügler

Neumaier

Coenen

2013

Labelled Comp Radiopharmac

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The D(4) receptor is of high interest for research and clinical application but puts high demands on appropriate radioligands to be useful tools for investigation. Search for adequate radioligands suitable for in vivo imaging is therefore still in progress. The potential neuroleptic drug 6-(4-[4-fluorobenzyl]piperazin-1-yl)benzodioxin shows high affinity and selectivity to the D(4) receptor. Derivatization of this lead structure by adding hydrophilic moieties was carried out in order to lower its lipophilicity what led to three new putative dopamine receptor D(4) ligands. A comprehensive description of the syntheses of standard compounds and corresponding labeling precursors is given which were obtained in satisfactory yields. Furthermore, the radiosyntheses by direct (18) F-labeling and build-up synthesis were compared. All derivatives of 6-(4-[4-fluorobenzyl]-piperazin-1-yl)benzodioxin were successfully synthesized in (18) F-labeled form with radiochemical yields of 9-35% and molar activities of 30-60 GBq/µmol using one-pot procedures.

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Section: Comparison Of Methodsmentioning

confidence: 99%

Labeling of benzodioxin piperazines with fluorine‐18 as prospective radioligands for selective imaging of dopamine D₄ receptors

Kügler

Neumaier

Coenen

2013

Labelled Comp Radiopharmac

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“…The first molecule that was 18 F-labelled via this approach for clinical application and is in use still today [109,110] has been the serotonergic 5-HT2A receptor ligand [ 18 F]altanserin [111,112]. Like in many other complex molecules with activated carbocyclic aromatic positions [113], the keto group in para-position activates the 18 Ffor-NO2 exchange employed here, and the one-step synthesis is performed without the need of a protecting group. However, the reaction leads to a side product, which necessitates an extensive HPLC purification [114].…”

Section: Progress In Aromatic Nucleophilic 18 F-fluorinationmentioning

confidence: 99%

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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“…This is true for the C-F bond too. or nitro groups or special combinations of both act as leaving groups [162] . For aromatic nucleophilic substitution reactions, the -N(Me 3 ) + group is preferred because it usually allows more reproducible radiosynthesis with higher RCYs.…”

Section: Preparation Of Labeling Precursors and Radio Labelingmentioning

confidence: 99%

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

2014

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Positron emission tomography (PET) is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including geneticallyengineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.Keywords: Alzheimer's disease; autoradiography; blood-brain barrier; brain tumor; cholinergic system; kinetic modeling; metabolism; molecular imaging; neurodegeneration; positron emission tomography; precursor; psychiatric disorder; radiotracer; sigma receptor ·Review· IntroductionPositron emission tomography (PET) is an in vivo molecular imaging tool widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. Positron-emitting radionuclide-labeled substances allow the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems by highly sensitive coincidence-detection [1] . This is based on 511 keV photons (gamma radiation) originating from positronelectron annihilation. PET differs in that aspect from other modalities such as single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and ultrasound. Because of their high sensitivity (~10 -9 to 10 -12 M) PET and SPECT offer advantages over the other methods. Therefore, in the past, they were the only modalities that allowed noninvasive imaging of biochemical receptor sites. Nowadays, the other imaging modalities compete in that aspect although precise absolute quantitation in terms of biochemical parameters has not been achieved yet. fusion accuracy, provides an advanced diagnostic tool and research platform [2,3] .PET and SPECT use biomolecules as probes, labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. According to the concept developed by George ...

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Nucleophilic 18F-Fluorination of Complex Molecules in Activated Carbocyclic Aromatic Position

Cited by 13 publications

References 0 publications

Labeling of benzodioxin piperazines with fluorine‐18 as prospective radioligands for selective imaging of dopamine D₄ receptors

Labeling of benzodioxin piperazines with fluorine‐18 as prospective radioligands for selective imaging of dopamine D₄ receptors

18F-labelling innovations and their potential for clinical application

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

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Nucleophilic 18F-Fluorination of Complex Molecules in Activated Carbocyclic Aromatic Position

Cited by 13 publications

References 0 publications

Labeling of benzodioxin piperazines with fluorine‐18 as prospective radioligands for selective imaging of dopamine D4 receptors

Labeling of benzodioxin piperazines with fluorine‐18 as prospective radioligands for selective imaging of dopamine D4 receptors

18F-labelling innovations and their potential for clinical application

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

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Product

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Labeling of benzodioxin piperazines with fluorine‐18 as prospective radioligands for selective imaging of dopamine D₄ receptors

Labeling of benzodioxin piperazines with fluorine‐18 as prospective radioligands for selective imaging of dopamine D₄ receptors