Molecular imaging of σ receptors: synthesis and evaluation of the potent σ1 selective radioligand [18F]fluspidine

Fischer, Steffen; Wiese, Christian; Maestrup, Eva Grosse; Hiller, Achim; Deuther‐Conrad, Winnie; Scheunemann, Matthias; Schepmann, Dirk; Steinbach, Jörg; Wünsch, Bernhard; Brust, Peter

doi:10.1007/s00259-010-1658-z

Cited by 63 publications

(112 citation statements)

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“…Racemic 18 F-fluspidine shows a high selectivity for the s 1 R over the s 2 R (1,300-fold), the vesicular acetylcholine transporter (2,400-fold), the emopamil binding protein (360-fold), and further off-target proteins (.600-fold) (16). By contrast, nonnegligible affinity (50 nM) of SA4503 to the vesicular acetylcholine transporter has been observed (19).…”

Section: Discussionmentioning

confidence: 95%

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Distinctive In Vivo Kinetics of the New σ₁ Receptor Ligands (R)-(+)- and (S)-(–)-¹⁸F-Fluspidine in Porcine Brain

et al. 2014

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Section: Discussionmentioning

confidence: 95%

“…We have recently synthesized 4 series of spirocyclic benzofurans (11)(12)(13)(14) and selected 4 derivatives (K i 5 0.59-1.4 nM) for 18 F labeling and evaluation as PET tracers (13)(14)(15)(16). Although all appear to be applicable for neuroimaging of s 1 Rs, a 2-fluoroethyl homolog, named 18 F-fluspidine, was most suitable (2).…”

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confidence: 99%

Distinctive In Vivo Kinetics of the New σ₁ Receptor Ligands (R)-(+)- and (S)-(–)-¹⁸F-Fluspidine in Porcine Brain

et al. 2014

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“…Very high selectivity towards the VAChT has been found, excluding cross-reactions with this target [139] .…”

Section: New Compoundsmentioning

confidence: 84%

“…However, structural modifi cation was needed to introduce fl uorine in a suitable labeling position. Accordingly, various series of derivatives have been synthetized to select those with the highest affinity, selectivity, and in vitro metabolic stability [133][134][135][136][137][138] .Very high selectivity towards the VAChT has been found, excluding cross-reactions with this target [139] . …”

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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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“…(Figure 1) In the capsaicin assay, an animal model for neuropathic pain, the benzofuran 1a sowed promising analgesic activity. [23][24][25] Starting with the high  1 affinity and selectivity of 1a a series of homologous fluoroalkyl derivatives was designed as PET (positron emission tomography) tracers [26][27][28][29][30][31] resulting in the fluoroethyl derivative fluspidine (2). [ 18 …”

Section: Introductionmentioning

confidence: 99%

Oxa-Pictet–Spengler reaction as key step in the synthesis of novel σ receptor ligands with 2-benzopyran structure

Knappmann

Schepmann

Wünsch

2016

Bioorganic & Medicinal Chemistry

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Molecular imaging of σ receptors: synthesis and evaluation of the potent σ1 selective radioligand [18F]fluspidine

Cited by 63 publications

References 58 publications

Distinctive In Vivo Kinetics of the New σ₁ Receptor Ligands (R)-(+)- and (S)-(–)-¹⁸F-Fluspidine in Porcine Brain

Distinctive In Vivo Kinetics of the New σ₁ Receptor Ligands (R)-(+)- and (S)-(–)-¹⁸F-Fluspidine in Porcine Brain

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

Oxa-Pictet–Spengler reaction as key step in the synthesis of novel σ receptor ligands with 2-benzopyran structure

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Molecular imaging of σ receptors: synthesis and evaluation of the potent σ1 selective radioligand [18F]fluspidine

Cited by 63 publications

References 58 publications

Distinctive In Vivo Kinetics of the New σ1 Receptor Ligands (R)-(+)- and (S)-(–)-18F-Fluspidine in Porcine Brain

Distinctive In Vivo Kinetics of the New σ1 Receptor Ligands (R)-(+)- and (S)-(–)-18F-Fluspidine in Porcine Brain

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

Oxa-Pictet–Spengler reaction as key step in the synthesis of novel σ receptor ligands with 2-benzopyran structure

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Distinctive In Vivo Kinetics of the New σ₁ Receptor Ligands (R)-(+)- and (S)-(–)-¹⁸F-Fluspidine in Porcine Brain

Distinctive In Vivo Kinetics of the New σ₁ Receptor Ligands (R)-(+)- and (S)-(–)-¹⁸F-Fluspidine in Porcine Brain