Radiochemical synthesis and in vivo evaluation of [18F]AZ11637326: An agonist probe for the α7 nicotinic acetylcholine receptor

Ravert, Hayden T.; Dorff, Peter N.; Foss, Catherine A.; Mease, Ronnie C.; Fan, Hong; Holmquist, Christopher R.; Phillips, Eifion D.; McCarthy, Dennis J.; Heys, J. Richard; Holt, Daniel P.; Wang, Yuchuan; Endres, Christopher J.; Dannals, Robert F.; Pomper, Martin G.

doi:10.1016/j.nucmedbio.2013.04.005

Cited by 18 publications

(10 citation statements)

References 33 publications

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“…In order to determine α7-nAChR selectivity of new compounds vs. other nAChR subtypes, binding assays for the main cerebral heteromeric nAChR subtypes (α2β2-, α2β4-, α3β2-, α3β4-, α4β2-, α4β4-) were also performed (Table 2). In addition, because α7-nAChR shares 30% homology with the 5-HT 3 receptor and first generation α7-nAChR radioligands exhibited low α7-nAChR/5-HT 3 selectivity, 27 the in vitro binding affinity at the 5-HT 3 receptor was also determined for selected compounds of our series (Table 2). …”

Section: Resultsmentioning

confidence: 99%

Derivatives of Dibenzothiophene for Positron Emission Tomography Imaging of α7-Nicotinic Acetylcholine Receptors

et al. 2013

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A new series of derivatives of 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)dibenzo[b,d]thiophene 5,5-dioxide with high binding affinities and selectivity for α7-nicotinic acetylcholine receptors (α7-nAChRs) (Ki = 0.4 – 20 nM) has been synthesized for PET imaging of α7-nAChRs. Two radiolabeled members of the series [18F]7a (Ki = 0.4 nM) and [18F]7c (Ki = 1.3 nM) were synthesized. [18F]7a and [18F]7c readily entered the mouse brain and specifically labeled α7-nAChRs. The α7-nAChR selective ligand 1 (SSR180711) blocked the binding of [18F]7a in the mouse brain in a dose-dependent manner. The mouse blocking studies with non-α7-nAChR CNS drugs demonstrated that [18F]7a is highly α7-nAChR selective. In agreement with its binding affinity the binding potential of [18F]7a (BPND = 5.3 – 8.0) in control mice is superior to previous α7-nAChR PET radioligands. Thus, [18F]7a displays excellent imaging properties in mice and has been chosen for further evaluation as a potential PET radioligand for imaging of α7-nAChR in non-human primates.

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Section: Resultsmentioning

confidence: 99%

Derivatives of Dibenzothiophene for Positron Emission Tomography Imaging of α7-Nicotinic Acetylcholine Receptors

et al. 2013

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“…The most recent α7-nAChR PET radioligands, [ 18 F]AZ11637326[53, 54], [ 11 C]NS14492[55] and [ 18 F]NS10743[56, 57] (Fig. 3), exhibited some specific binding in the brains of lab animals, but their specificities were also insufficient for human PET.…”

Section: Initial Pet Radioligands For α7-nachrsmentioning

confidence: 99%

“…Recent α7-nAChR PET radioligands, [ 18 F]AZ11637326[53, 54], [ 11 C]NS14492[55], [ 18 F]NS10743[56, 57] and [ 11 C]A-752274[58]. …”

Section: Figmentioning

confidence: 99%

Development of [ 18 F]ASEM, a specific radiotracer for quantification of the α7-nAChR with positron-emission tomography

Horti¹

2015

Biochemical Pharmacology

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The alpha-7 subtype of the nicotinic acetylcholine receptor (α7-nAChR) is fundamental to physiology; it mediates various brain functions and represents an important target for drug discovery. Exploration of the brain nicotinic acetylcholine receptors (nAChRs) using positron-emission tomography (PET) will make it possible to better understand the important role of this receptor and to study its involvement in schizophrenia, bipolar disorder, Alzheimer's and Parkinson's diseases, drug dependence, inflammation and many other disorders and simplify the development of nicotinic drugs for treatment of these disorders. Until recently, PET imaging of α7-nAChRs has been impeded by the absence of good radiotracers. This review describes various endeavors to develop α7-nAChR PET tracers by several research groups including the author’s group. Most initial PET tracers for imaging α7-nAChRs did not exhibit suitable imaging properties due to their low specific binding. Recently discovered [18F]ASEM is the first highly specific α7-nAChR radioligand and it was recently translated to human PET imaging.

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“…Cytisine is a partial nicotinic agonist selective for α4β2-nAChR and other β2-containing heteromeric nAChR subtypes with very low α7-nAChR binding affinity[3, 30, 37] and ondansetron is a selective 5-HT 3 antagonist[38]. Most previous α7-nAChR PET and SPECT radiotracers suffered a lack of selectivity versus 5-HT 3 and/or the second major nicotinic receptor subtype α4β2-nAChR[39]. In this study, neither cytisine nor ondansetron reduced the accumulation of [ 125 I]iodo-ASEM radioactivity in the mouse brain when compared with mice injected with vehicle (Fig.…”

Section: Resultsmentioning

confidence: 99%

[ 125 I]Iodo-ASEM, a specific in vivo radioligand for α7-nAChR

Gao

Mease

Olson

et al. 2015

Nuclear Medicine and Biology

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[125I]Iodo-ASEM, a new radioligand with high affinity and selectivity for α7-nAChRs (Ki = 0.5 nM; α7/α4β2 = 3,414), has been synthesized in radiochemical yield of 33 ± 6% from the corresponding di-butyltriazene derivative and at high specific radioactivity (1,600 Ci/mmol; 59.2 MBq/μmol). [125I]Iodo-ASEM readily entered the brains of normal CD-1 mice and specifically and selectively labeled cerebral α7-nAChRs. [125I]iodo-ASEM is a new useful tool for studying α7-nAChR.

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Radiochemical synthesis and in vivo evaluation of [18F]AZ11637326: An agonist probe for the α7 nicotinic acetylcholine receptor

Cited by 18 publications

References 33 publications

Derivatives of Dibenzothiophene for Positron Emission Tomography Imaging of α7-Nicotinic Acetylcholine Receptors

Derivatives of Dibenzothiophene for Positron Emission Tomography Imaging of α7-Nicotinic Acetylcholine Receptors

Development of [ 18 F]ASEM, a specific radiotracer for quantification of the α7-nAChR with positron-emission tomography

[ 125 I]Iodo-ASEM, a specific in vivo radioligand for α7-nAChR

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