Synthesis, quality control and tissue distribution of 2-[18F]-nicotinic acid diethylamide, a potential agent for regional cerebral function studies

Knust, E. J.; Müller‐Platz, C.; Schüller, Manfred

doi:10.1007/bf02520379

Cited by 18 publications

(2 citation statements)

References 13 publications

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“…Nicotinic acetylcholine receptors (nAChR) are proposed to play key roles in the central nervous system, in particular for Parkinson’s disease and Alzheimer’s disease (AD), tobacco dependency and schizophrenia, in addition to numerous other disorders; this has promoted much research into selective radioligands to study these receptors. − The earliest published data on use of S N Ar for labeling on heteroarenes with [ 18 F]fluoride are by Knust and co-workers, who report the synthesis of 2-[ 18 F]fluoro- and 6-[ 18 F]fluoro-nicotinic acid diethylamide by displacement of a chloride leaving group. − The reaction conditions are extremely harsh, with 2-chloro- or 6-chloro-nicotinic acid diethyl amide with [ 18 F]KF being heated to 250 °C in an acetamide melt, for approximately 30 min in a sealed bulb. Higher temperatures and longer reactions times led to lower RCYs presumed to be the result of decomposition.…”

Section: F-fluorination Of (Hetero)arenes Using An [18f]f¯ Sourcementioning

confidence: 99%

¹⁸F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography

2016

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Diverse radiochemistry is an essential component of nuclear medicine; this includes imaging techniques such as positron emission tomography (PET). As such, PET can track diseases at an early stage of development, help patient care planning through personalized medicine and support drug discovery programs. Fluorine-18 is the most frequently used radioisotope in PET radiopharmaceuticals for both clinical and preclinical research. Its physical and nuclear characteristics (97% β(+) decay, 109.8 min half-life, 635 keV positron energy) and high specific activity make it an attractive nuclide for labeling and molecular imaging. Arenes and heteroarenes are privileged candidates for (18)F-incorporation as they are metabolically robust and therefore widely used by medicinal chemists and radiochemists alike. For many years, the range of (hetero)arenes amenable to (18)F-fluorination was limited by the lack of chemically diverse precursors, and of radiochemical methods allowing (18)F-incorporation in high selectivity and efficiency (radiochemical yield and purity, specific activity, and radio-scalability). The appearance of late-stage fluorination reactions catalyzed by transition metal or small organic molecules (organocatalysis) has encouraged much research on the use of these activation manifolds for (18)F-fluorination. In this piece, we review all of the reactions known to date to install the (18)F substituent and other key (18)F-motifs (e.g., CF3, CHF2, OCF3, SCF3, OCHF2) of medicinal relevance onto (hetero)arenes. The field has changed significantly in the past five years, and the current trend suggests that the radiochemical space available for PET applications will expand rapidly in the near future.

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Section: F-fluorination Of (Hetero)arenes Using An [18f]f¯ Sourcementioning

confidence: 99%

¹⁸F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography

2016

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“…9 Acetamide should on the other hand not decrease the RCY, as it is a known [ 18 F]fluoride labelling solvent. [10][11][12] Acetamide is, however, a toxic carcinogen, and its formation is necessary to understand and control to an acceptable low level in the final product.…”

Section: Introductionmentioning

confidence: 99%

Degradation of acetonitrile in eluent solutions for [¹⁸F]fluoride PET chemistry: impact on radiosynthesis of [¹⁸F]FACBC and [¹⁸F]FDG

Svadberg

Wickstrøm

Hjelstuen

2012

Labelled Comp Radiopharmac

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In [18F]fluoride chemistry, an eluent solution containing a weak aqueous base is used to release [18F]fluoride after adsorption on an anion exchange resin. Traditionally, the eluent solution is freshly prepared, but modern PET tracer manufacturers may utilize the benefits of preparing bulk solutions or prefilled vials for storage. We discovered that typical eluent solutions containing kryptofix and K2CO3 in aqueous acetonitrile degraded upon storage. Acetonitrile will at alkaline pH hydrolyse to acetamide and ammonium acetate. Acetate may serve as a competing nucleophile to [18F]fluoride. Eluent solutions used in the synthesis of [18F]FACBC and [18F]FDG generated mg/ml levels of acetamide and ammonium acetate during storage at room temperature or above. The synthesis of [18F]FACBC was prone to eluent degradation, with gradual reduction of radiochemical yield (RCY) from 62.5% to 44.7% during 12 months of storage at 30 °C. The synthesis of [18F]FDG was only affected when the eluent was stored at 50 °C, reducing the RCY from 86.8% to 66.7% after 3 months of storage. For degradation effects to be avoided, an alternative eluent solution with no acetonitrile was investigated in the synthesis of [18F]FACBC. A methanol‐based eluent was successfully made, showing no degradation and unchanged RCY after 6 months of storage at 50 °C. Copyright © 2012 John Wiley & Sons, Ltd.

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N.C.A. [¹⁸F]‐labelling of aliphatic compounds in high yields via aminopolyether ‐ supported nucleophilic substitution

Block

Klatte

Knöchel

et al. 1986

Labelled Comp Radiopharmac

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The nucleophilic introduction of n.c.a. ‐ [18F]‐fluoride into alkanes and carboxylic acids using anion activation by macrocyclic polyethers was investigated. The reactions carried out in the presence of the bicyclic aminopolyether APE 2.2.2. gave rise to high radiochemical yields (40‐65 %) under mild conditions. Important for the successful 18F‐labelling is a suitable cation/polyether couple, which leads to an unsolvated [18F]‐fluoride in a dipolar aprotic solvent and ensures a high ion concentration, thus enhancing the reactivity. Reaction parameters, such as concentration of substrate and APE, the influence of cation, anion and water were studied and optimised.

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Synthesis, quality control and tissue distribution of 2-[18F]-nicotinic acid diethylamide, a potential agent for regional cerebral function studies

Cited by 18 publications

References 13 publications

¹⁸F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography

¹⁸F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography

Degradation of acetonitrile in eluent solutions for [¹⁸F]fluoride PET chemistry: impact on radiosynthesis of [¹⁸F]FACBC and [¹⁸F]FDG

N.C.A. [¹⁸F]‐labelling of aliphatic compounds in high yields via aminopolyether ‐ supported nucleophilic substitution

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Synthesis, quality control and tissue distribution of 2-[18F]-nicotinic acid diethylamide, a potential agent for regional cerebral function studies

Cited by 18 publications

References 13 publications

18F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography

18F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography

Degradation of acetonitrile in eluent solutions for [18F]fluoride PET chemistry: impact on radiosynthesis of [18F]FACBC and [18F]FDG

N.C.A. [18F]‐labelling of aliphatic compounds in high yields via aminopolyether ‐ supported nucleophilic substitution

Contact Info

Product

Resources

About

¹⁸F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography

¹⁸F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography

Degradation of acetonitrile in eluent solutions for [¹⁸F]fluoride PET chemistry: impact on radiosynthesis of [¹⁸F]FACBC and [¹⁸F]FDG

N.C.A. [¹⁸F]‐labelling of aliphatic compounds in high yields via aminopolyether ‐ supported nucleophilic substitution