Radiosynthesis and first evaluation in mice of [18F]NS14490 for molecular imaging of α7 nicotinic acetylcholine receptors

Rötering, Sven; Scheunemann, Matthias; Fischer, Steffen; Hiller, Achim; Peters, Dan; Deuther‐Conrad, Winnie; Brust, Peter

doi:10.1016/j.bmc.2013.02.018

Cited by 29 publications

(21 citation statements)

References 30 publications

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“…A new synthesis method for the nAChR radiotracer [ 18 F]NS14490 ( Figure 2 , compound o) proposed by Rotering et al allows for the direct nucleophilic substitution of the precursor, resulting in 70% radiochemical yield. 73 This tracer demonstrated high target affinity as well as selectivity in vitro for the α7 receptor subtype. In rodent PET studies, low brain uptake for the tracer was observed, but the compound had high stability in brain tissue and in plasma.…”

Section: Nicotinic Acetylcholine Receptormentioning

confidence: 97%

Selected PET Radioligands for Ion Channel Linked Neuroreceptor Imaging: Focus on GABA, NMDA and nACh Receptors

Kassenbrock¹,

Vasdev²,

Liang

2016

CTMC

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Positron emission tomography (PET) neuroimaging of ion channel linked receptors is a developing area of preclinical and clinical research. The present review focuses on recent advances with radiochemistry, preclinical and clinical PET imaging studies of three receptors that are actively pursued in neuropsychiatric drug discovery: namely the γ-aminobutyric acid-benzodiazapine (GABA) receptor, nicotinic acetylcholine receptor (nAChR), and N-methyl-d-aspartate (NMDA) receptor. Recent efforts to develop new PET radioligands for these targets with improved brain uptake, selectivity, stability and pharmacokinetics are highlighted.

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Section: Nicotinic Acetylcholine Receptormentioning

confidence: 97%

Selected PET Radioligands for Ion Channel Linked Neuroreceptor Imaging: Focus on GABA, NMDA and nACh Receptors

Kassenbrock¹,

Vasdev²,

Liang

2016

CTMC

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“…Further studies are needed for both radioligands to be applied in human subjects, such as in radiation dosimetry and toxicology studies. [ 18 F]NS14490 is a recently reported radiolabeled 1,4-diazabicyclo[3.2.2] nonane derivative [87]. Researchers successfully radiosynthesized [ 18 F]NS14490 using both approaches.…”

Section: Significance Of Nachrs Pet Imagingmentioning

confidence: 97%

Neural nAChRs PET imaging probes

Yin

2014

Nuclear Medicine Communications

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There have been a number of attempts to study PET radioligands for imaging nicotinic acetylcholine receptors (nAChRs) in the human brain, and the most successful tracers found are radioligands for imaging α4β2-nAChRs, which is the main cerebral nAChRs subtype. C-Nicotine and 2-[F]FA have been applied in many studies in humans. However, neither is entirely ideal and efforts have been made to develop radioligands with optimized imaging properties. Only a few reports have been published on radioligands for α7-nAChRs imaging, another important cerebral nAChRs subtype. This paper will review the development of PET radioligands for imaging cerebral nAChRs.

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“…Consequently, low brain uptake in rodents does not necessarily forecast the uptake in other species like humans. For example, the brain uptake of the high-affi nity and selective α7 nAChR ligand [ 18 F]NS14492 is ~10-times higher in pigs than in mice, suggesting suitability for human brain imaging [222] . Similar species differences between rats, guinea pigs, and monkeys have been reported for the [223] .…”

Section: Proof Of Target-specifi C Binding In Animalsmentioning

confidence: 99%

“…Cohen et al 2000 [57] Opioid receptor: unselective [ 18 F]fl uorethyldiprenorphine Baumgärtner et al 2006 [58] Neuropeptide [60] Serotonin receptor: 5-HT 1A [carbonyl- 11 C]WAY-100635 Parsey et al 2000 [61] Serotonin receptor: 5-HT 1A [carbonyl-11 C]DWAY Andree et al 2002 [62] Serotonin receptor: 5-HT 1A [ 11 C]CPC- 222 Houle et al 1997 [63] Serotonin receptor: 5-HT 1A [ 11 C]CUMI- 101 Milak et al 2010 [64] Serotonin receptor: [66] Serotonin receptor: 5-HT 1B [ 11 C]P943 Gallezot et al 2010 [67] Serotonin receptor: 5-HT 1B [ 11 C]AZ10419369 Varnäs et al 2011 [68] Serotonin receptor: 5-HT 1B [ 11 C]P943 Murrough et al 2011 [69] Serotonin receptor: 5-HT 2A [ 11 C]MDL100907 Hinz et al 2007 [70] Serotonin receptor: 5-HT 2A [ 18 F]altanserin Rosier et al 1996 [71] Serotonin receptor: 5-HT 2A [ 18 F]deuteroaltanserin Van Dyck et al 2000 [72] Serotonin receptor: 5-HT 2A [ 18 F]setoperone Trichard et al 1998 [73] Serotonin receptor: 5-HT 2A [ 18 F]Cimbi-36 Ettrup et al 2014 [74] Serotonin receptor: 5-HT 4 [ 11 C]SB207145 Marner et al 2009 [75] Serotonin receptor: 5-HT 6 [ 11 C]GSK215083 Parker et al 2012 [76] Sigma receptor: σ 1 [ 11 C]SA4503 Mishina et al 2005 [77] Sigma receptor: σ 1 [ 18 F]FPS Waterhouse et al 2004 [78] Translocator protein (TSPO) b [ 11 C]PK11195 Junck et al 1989 [79] Translocator protein (TSPO) (R)-[ 11 C]PK11195 Banati et al 1999 [80] Translocator protein (TSPO) [ 11 C]PBR28 Brown et al 2007 [81] Translocat...…”

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confidence: 99%

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

2014

Self Cite

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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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Radiosynthesis and first evaluation in mice of [18F]NS14490 for molecular imaging of α7 nicotinic acetylcholine receptors

Cited by 29 publications

References 30 publications

Selected PET Radioligands for Ion Channel Linked Neuroreceptor Imaging: Focus on GABA, NMDA and nACh Receptors

Selected PET Radioligands for Ion Channel Linked Neuroreceptor Imaging: Focus on GABA, NMDA and nACh Receptors

Neural nAChRs PET imaging probes

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

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