Radioligand Development for PET Imaging of the Vesicular Acetylcholine Transporter (VAChT) in the Brain

Wenzel, Barbara; Deuther‐Conrad, Winnie; Scheunemann, Matthias; Brust, Peter

doi:10.1007/978-3-030-53176-8_32

Cited by 2 publications

(5 citation statements)

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“…VAChT is an approximately 500-amino-acid polypeptide uniquely present in cholinergic nerve terminals of the central and peripheral nervous system and corresponding closely to choline acetyltransferase (9).…”

Section: Structure and Distribution Of Vachtmentioning

confidence: 99%

“…The development of vesamicol derivatives showing high affinity to VAChT and high selectivity over off-targets such as s-receptors was challenging. Several vesamicol-, trozamicol-, and benzovesamicol-based PET ligands, as well as morpholinovesamicols and other vesamicol analogs, were developed and tested preclinically (9). Only the PET ligand (2)-18 Ffluoroethoxybenzovesamicol ( 18 F-FEOBV) (Table 1; Fig.…”

Section: Radioligands For Imaging Vachtmentioning

confidence: 99%

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PET Imaging of Cholinergic Neurotransmission in Neurodegenerative Disorders

et al. 2022

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As a neuromodulator, the neurotransmitter acetylcholine plays an important role in cognitive, mood, locomotor, sleep/wake, and olfactory functions. In the pathophysiology of most neurodegenerative diseases, such as Alzheimer disease (AD) or Lewy body disorder (LBD), cholinergic receptors, transporters, or enzymes are involved and relevant as imaging targets. The aim of this review is to summarize current knowledge on PET imaging of cholinergic neurotransmission in neurodegenerative diseases. For PET imaging of presynaptic vesicular acetylcholine transporters (VAChT), (2)-18 F-fluoroethoxybenzovesamicol ( 18 F-FEOBV) was the first PET ligand that could be successfully translated to clinical application. Since then, the number of 18 F-FEOBV PET investigations on patients with AD or LBD has grown rapidly and provided novel, important findings concerning the pathophysiology of AD and LBD. Regarding the a4b2 nicotinic acetylcholine receptors (nAChRs), various second-generation PET ligands, such as 18 F-nifene, 18

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Section: Structure and Distribution Of Vachtmentioning

confidence: 99%

Section: Radioligands For Imaging Vachtmentioning

confidence: 99%

PET Imaging of Cholinergic Neurotransmission in Neurodegenerative Disorders

et al. 2022

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“…13 The latter were obtained from histologically delineated ChBF subareas of a postmortem brain and its corresponding MRI coordinates, allowing projection into MNI standard space. From these subareas, the following were kept because of their relevance in AD: (1) the cholinergic neurons nuclei of the medial septum (Ch1) and vertical limb of the diagonal band of Broca (Ch2), taken together (Ch1/2), as they both provide the cholinergic innervation for the whole hippocampal complex; (2) the nucleus basalis of Meynert (Ch4), which projects to the entire cerebral cortex. 14,15 The latter Ch4 nucleus was further subdivided into three components.…”

Section: Pet and Mri Data Processingmentioning

confidence: 99%

“…Several PETradiotracers have been developed to quantify in vivo this cortical cholinergic denervation; so far, 18 F-fluroethoxybenzovesamicol ([ 18 F]-FEOBV) seems to be the most sensitive and reliable one to assess that parameter. 1 This radiotracer exhibits a very high binding affinity and selectivity for the vesicular acetylcholine transporter, 2 a glycoprotein found essentially in cholinergic synapses. PET imaging with [ 18 F]-FEOBV was found sensitive to even very subtle cholinergic denervation resulting from selective basal forebrain or mesopontine lesions.…”

Section: Introductionmentioning

confidence: 99%

“…Alzheimer's disease (AD) is characterized by a progressive degeneration of the basal forebrain cholinergic neurons, resulting in a severe cholinergic denervation of the whole cortical mantle. Several PET‐radiotracers have been developed to quantify in vivo this cortical cholinergic denervation; so far, 18 F‐fluroethoxybenzovesamicol ([ 18 F]‐FEOBV) seems to be the most sensitive and reliable one to assess that parameter 1 . This radiotracer exhibits a very high binding affinity and selectivity for the vesicular acetylcholine transporter, 2 a glycoprotein found essentially in cholinergic synapses.…”

Section: Introductionmentioning

confidence: 99%

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FEOBV‐PET to quantify cortical cholinergic denervation in AD: Relationship to basal forebrain volumetry

Aghourian

Aumont

Grothe

et al. 2021

Journal of Neuroimaging

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Background and Purpose: Fluorine-18-fluoroethoxybenzovesamicol([ 18 F]-FEOBV) is a PET radiotracer previously used in neurodegenerative diseases to quantify brain cholinergic denervation. The current exploratory study aimed at verifying the reliability of such an approach in Alzheimer's disease (AD) by demonstrating its concordance with MRI volumetry of the cholinergic basal forebrain (ChBF). Methods: The sample included 12 participants evenly divided between healthy volunteers and patients with AD. All participants underwent MRI ChBF volumetry and PET imaging with [ 18 F]-FEOBV. Comparisons were made between the two groups, and partial correlations were performed in the AD patients between [ 18 F]-FEOBV uptake in specific cortical regions of interest (ROIs) and volumetry of the corresponding ChBF subareas, which include the nucleus basalis of Meynert (Ch4), and the medial septum/vertical limb of the diagonal band of Broca (Ch1/2). Results: Patients with AD showed both lower ChBF-Ch4 volumetric values and lower [ 18 F]-FEOBV cortical uptake than healthy volunteers. Volumes of the Ch4 subdivision were significantly correlated with the [ 18 F]-FEOBV uptake values observed in the relevant ROIs. Volumes of the Ch1/2, which remains relatively unaffected in AD, did not correlate with [ 18 F]-FEOBV uptake in the hippocampus, nor in any cortical area. Conclusion: These results suggest that cortical cholinergic denervation as measured with [ 18 F]-FEOBV PET is proportional to ChBF atrophy measured by MRI-based volumetry, further supporting the reliability and validity of [ 18 F]-FEOBV PET to quantify cholinergic degeneration in AD.

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Radioligand Development for PET Imaging of the Vesicular Acetylcholine Transporter (VAChT) in the Brain

Cited by 2 publications

References 103 publications

PET Imaging of Cholinergic Neurotransmission in Neurodegenerative Disorders

PET Imaging of Cholinergic Neurotransmission in Neurodegenerative Disorders

FEOBV‐PET to quantify cortical cholinergic denervation in AD: Relationship to basal forebrain volumetry

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