Design, synthesis and preliminary evaluation of 18F-labelled 1,8-naphthyridin- and quinolin-2-one-3-carboxamide derivatives for PET imaging of CB2 cannabinoid receptor

Saccomanni, Giuseppe; Pascali, Giancarlo; Carlo, S. Del; Panetta, Daniele; Simone, Mariarosaria De; Bertini, Simone; Burchielli, Silvia; Digiacomo, Maria; Macchia, Marco; Manera, Clementina; Salvadori, Piero A.

doi:10.1016/j.bmcl.2015.04.055

Cited by 19 publications

(11 citation statements)

References 29 publications

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“…Similar problems occurred during the radiosynthesis of a PET tracer with OCD2 18 F moiety described by Hortala et al Due to a three-step radiosynthesis, the overall radiochemical yield was low (0.3 -1.6 %) [23]. The radiofluorination to yield [ 18 F]CB91 (5) also caused problems as an unexpected non-radioactive peak appeared in the HPLC chromatogram [24]. In 2016 the quinolineamine [ 18 F]MA3 (6) was reported, displaying high CB2 affinity and selectivity over the human CB1 receptor, but a rapid wash-out from brain ( Figure 1) [25].…”

Section: Introductionmentioning

confidence: 73%

Optimization of the metabolic stability of a fluorinated cannabinoid receptor subtype 2 (CB2) ligand designed for PET studies

Heimann

Börgel

Vries

et al. 2018

European Journal of Medicinal Chemistry

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The central CB receptor represents a promising target for the treatment of neuroinflammatory diseases as CB activation mediates anti-inflammatory effects. Recently, the F-18 labeled PET radiotracer [F]7a was reported, which shows high CB affinity and high selectivity over the CB subtype but low metabolic stability due to hydrolysis of the amide group. Based on these findings twelve bioisosteres of 7a were synthesized containing a non-hydrolysable functional group instead of the amide group. The secondary amine 23a (K = 7.9 nM) and the ketone 26a (K = 8.6 nM) displayed high CB affinity and CB:CB selectivity in in vitro radioligand binding studies. Incubation of 7a, 23a and 26a with mouse liver microsomes and LC-quadrupole-MS analysis revealed a slightly higher metabolic stability of secondary amine 23a, but a remarkably higher stability of ketone 26a in comparison to amide 7a. Furthermore, a logD value of 5.56 ± 0.08 was determined for ketone 26a by micro shake-flask method and LC-MS quantification.

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Section: Introductionmentioning

confidence: 73%

Optimization of the metabolic stability of a fluorinated cannabinoid receptor subtype 2 (CB2) ligand designed for PET studies

Heimann

Börgel

Vries

et al. 2018

European Journal of Medicinal Chemistry

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“…In this case, radiochemistry optimization and later high‐activity radiotracer production were performed in a commercial microfluidic apparatus (NanoTek, Advion). [ 18 F]CB91 was obtained as a mixture of cis and trans isomers in 42% yield from reactions in DMSO at 190°C using about 25 seconds of microreactor residence time (Table , entry 10) . CB91 contains a fluorine substituent on a deactivated phenyl ring and therefore would have been a poor candidate for direct labeling through a classical S N Ar reaction.…”

Section: Discussionmentioning

confidence: 99%

Hypervalent aryliodine compounds as precursors for radiofluorination

Pike

2018

Labelled Comp Radiopharmac

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Over the last 2 decades or so, hypervalent iodine compounds, such as diaryliodonium salts and aryliodonium ylides, have emerged as useful precursors for labeling homoarenes and heteroarenes with no-carrier-added cyclotron-produced [ F]fluoride ion (t = 109.8 min). They permit rapid and effective radiofluorination at electron-rich as well as electron-deficient aryl rings, and often with unrestricted choice of ring position. Consequently, hypervalent aryliodine compounds have found special utility as precursors to various small-molecule F-labeling synthons and to many radiotracers for biomedical imaging with positron emission tomography. This review summarizes this advance in radiofluorination chemistry, with emphasis on precursor synthesis, radiofluorination mechanism, method scope, and method application.

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“…CB 2 R imaging in patients with Alzheimer's disease Emerging evidence indicates the involvement of CB 2 R and increased levels of complements, cytokines, and chemokines in the brain of patients with AD. Reactive astrocytes, activated microglia, and upregulated CB 2 R were observed in the vicinity of Aβ plaques in post-mortem AD mouse model brains and patients with AD [62,[75][76][77][78][79][80][81][82][83][84][85][86][87][88]. PET using [ 11 C]NE40 showed reduced signal along with Aβ [47].…”

Section: Potential Clinical Use Of Cb 2 R Pet Imaging Of Cns Inflammamentioning

confidence: 98%

Positron emission tomography of type 2 cannabinoid receptors for detecting inflammation in the central nervous system

Ametamey

2018

Acta Pharmacol Sin

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Cannabinoid receptor CB (CBR) is upregulated on activated microglia and astrocytes in the brain under inflammatory conditions and plays important roles in many neurological diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. The advent of positron emission tomography (PET) using CBR radiotracers has enabled the visualization of CBR distribution in vivo in animal models of central nervous system inflammation, however translation to humans has been less successful. Several novel CBR radiotracers have been developed and evaluated to quantify microglial activation. In this review, we summarize the recent preclinical and clinical imaging results of CBR PET tracers and discuss the prospects of CBR imaging using PET.

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Design, synthesis and preliminary evaluation of 18F-labelled 1,8-naphthyridin- and quinolin-2-one-3-carboxamide derivatives for PET imaging of CB2 cannabinoid receptor

Cited by 19 publications

References 29 publications

Optimization of the metabolic stability of a fluorinated cannabinoid receptor subtype 2 (CB2) ligand designed for PET studies

Optimization of the metabolic stability of a fluorinated cannabinoid receptor subtype 2 (CB2) ligand designed for PET studies

Hypervalent aryliodine compounds as precursors for radiofluorination

Positron emission tomography of type 2 cannabinoid receptors for detecting inflammation in the central nervous system

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