18F-labelled vesamicol derivatives: Syntheses and preliminary in vivo small animal positron emission tomography evaluation

Rogers, Gary A.; Stone‐Elander, Sharon; Ingvar, Martin; Eriksson, Lars; Parsons, Stanley M.; Widén, L.

doi:10.1016/0969-8051(94)90012-4

Cited by 31 publications

(12 citation statements)

References 25 publications

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“…However, (À)-vesamicol and most of its derivatives exhibit additional high affinity binding, especially to a-adrenoreceptors and s-receptors (Custers et al, 1997;Efange et al, 1995;Wannan et al, 1991). Several [ l8 F]-labeled VAChT radioligands have been synthesized including [ 18 F]NEFA (Rogers et al, 1994), [ 18 F]FBT (Mach et al, 1997), and (2R,3R)-5-[ 18 F]FEOBV (Mulholland et al, 1998) (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Ex vivo and in vivo evaluation of (2R,3R)‐5‐[¹⁸F]‐fluoroethoxy‐ and fluoropropoxy‐benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter

Giboureau

Emond

Fulton

et al. 2007

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Molecular imaging of the vesicular acetylcholine transporter (VAChT) using positron emission tomography (PET) may provide insights into early diagnosis and better understanding of Alzheimer's disease. We further characterized the VAChT ligand (2R,3R)-5-FEOBV (1) and developed new fluoropropoxy analogues. Ex vivo studies of the new nonradiolabeled analogues (2R,3R)-5-FPOBV (2) (k(D) = 0.7 nM) and (2S,3S)-5-FPOBV (3) (k(D) = 8.8 nM) were performed in rat brain and showed an enantioselective inhibition of (-)-5-[(125)I]-IBVM uptake in striatum, cortex, and hippocampus (e.g., 74% for 2 and only 54% for 3 in the cortex). Radiochemical procedures were developed to produce [(18)F]1 and [(18)F]2 as potential imaging agent for the VAChT. The radiochemistry was carried out in a one step procedure, with radiolabeling yields of 17 and 2.6% (range: 1-5.4), respectively, nondecay corrected with good specific activity: 124-338 GBq/micromol. The radiochemical purity was greater than 98%. The biological (ex vivo and in vivo) properties of these radioligands were evaluated in rats and showed a low (less then 0.1% of the injected dose) and homogeneous brain uptake. The in vivo PET study of [(18)F]2 performed in baboon also revealed rapid defluorination as the main problem. Therefore [(18)F]1 and [(18)F]2 appear to be unsuitable for in vivo imaging of the VAChT using PET.

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Section: Introductionmentioning

confidence: 99%

Ex vivo and in vivo evaluation of (2R,3R)‐5‐[¹⁸F]‐fluoroethoxy‐ and fluoropropoxy‐benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter

Giboureau

Emond

Fulton

et al. 2007

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“…This catalytic activity is crucial for the bioactivation of the acetanilide class of analgesic agents represented by paracetamol as the most important member [48]. Metabolic instability was also observed for aliphatic 18 F-labelled fluoroacetamides [13,49]. Their fate seems to be different from their aromatic counterparts in the way that they undergo defluorination at the α-methylene group rather than hydrolytic cleavage of the amide bond [13].…”

Section: Resultsmentioning

confidence: 99%

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

Löser¹,

Fischer²,

Hiller³

et al. 2013

Beilstein J. Org. Chem.

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Summary3-[18F]Fluoropropanesulfonyl chloride, a recently proposed prosthetic agent for fluorine-18 labelling, was prepared in a two-step radiosynthesis via 3-[18F]fluoropropyl thiocyanate as an intermediate. Two benzenesulfonate-based radiolabelling precursors were prepared by various routes. Comparing the reactivities of 3-thiocyanatopropyl nosylate and the corresponding tosylate towards [18F]fluoride the former proved to be superior accounting for labelling yields of up to 85%. Conditions for a reliable transformation of 3-[18F]fluoropropyl thiocyanate to the corresponding sulfonyl chloride with the potential for automation have been identified. The reaction of 3-[18F]fluoropropanesulfonyl chloride with eight different aliphatic and aromatic amines was investigated and the identity of the resulting 18F-labelled sulfonamides was confirmed chromatographically by comparison with their nonradioactive counterparts. Even for weakly nucleophilic amines such as 4-nitroaniline the desired radiolabelled sulfonamides were accessible in satisfactory yields owing to systematic variation of the reaction conditions. With respect to the application of the 18F-fluoropropansulfonyl group to the labelling of compounds relevant as imaging agents for positron emission tomography (PET), the stability of N-(4-fluorophenyl)-3-fluoropropanesulfonamide against degradation catalysed by carboxylesterase was investigated and compared to that of the analogous fluoroacetamide.

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“…(−)-[ 11 C]-Methylaminobenzovesamicol ((−)-[ 11 C]MABV ( 3 )) and (−)-[ 18 F]-N - ethyl - N - fluoroacetamidobenzovesamicol ((−)-[ 18 F]NEFA ( 4 )) . As benzovesamicol analogs with the amino group, (−)-[ 11 C]-methylaminobenzovesamicol ((−)-[ 11 C]MABV ( 3 )) [ 48 ] and (−)-[ 18 F]- N -ethyl- N -fluoroacetamidobenzovesamicol ((−)-[ 18 F]NEFA ( 4 )) [ 49 , 50 ] were reported. The accumulation of (−)-[ 11 C]MABV ( 3 ) in the striatum, the cortex, the hippocampus, and the cerebellum in mice 45 min after injection was 8.10, 3.99, 3.58, and 1.05 %ID/g, although the binding affinity (Ki) of (−)-[ 11 C]MABV ( 3 ) to VAChT and σ 1 and σ 2 receptors was not reported.…”

Section: Vacht Imaging Agent Based On Vesamicol Analogsmentioning

confidence: 99%

In Vivo and In Vitro Characteristics of Radiolabeled Vesamicol Analogs as the Vesicular Acetylcholine Transporter Imaging Agents

Ogawa

Shiba

2018

Contrast Media & Molecular Imaging

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The vesicular acetylcholine transporter (VAChT), a presynaptic cholinergic neuron marker, is a potential internal molecular target for the development of an imaging agent for early diagnosis of neurodegenerative disorders with cognitive decline such as Alzheimer's disease (AD). Since vesamicol has been reported to bind to VAChT with high affinity, many vesamicol analogs have been studied as VAChT imaging agents for the diagnosis of cholinergic neurodeficit disorder. However, because many vesamicol analogs, as well as vesamicol, bound to sigma receptors (σ1 and σ2) besides VAChT, almost all the vesamicol analogs have been shown to be unsuitable for clinical trials. In this report, the relationships between the chemical structure and the biological characteristics of these developed vesamicol analogs were investigated, especially the in vitro binding profile and the in vivo regional brain accumulation.

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18F-labelled vesamicol derivatives: Syntheses and preliminary in vivo small animal positron emission tomography evaluation

Cited by 31 publications

References 25 publications

Ex vivo and in vivo evaluation of (2R,3R)‐5‐[¹⁸F]‐fluoroethoxy‐ and fluoropropoxy‐benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter

Ex vivo and in vivo evaluation of (2R,3R)‐5‐[¹⁸F]‐fluoroethoxy‐ and fluoropropoxy‐benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

In Vivo and In Vitro Characteristics of Radiolabeled Vesamicol Analogs as the Vesicular Acetylcholine Transporter Imaging Agents

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18F-labelled vesamicol derivatives: Syntheses and preliminary in vivo small animal positron emission tomography evaluation

Cited by 31 publications

References 25 publications

Ex vivo and in vivo evaluation of (2R,3R)‐5‐[18F]‐fluoroethoxy‐ and fluoropropoxy‐benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter

Ex vivo and in vivo evaluation of (2R,3R)‐5‐[18F]‐fluoroethoxy‐ and fluoropropoxy‐benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter

Use of 3-[18F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

In Vivo and In Vitro Characteristics of Radiolabeled Vesamicol Analogs as the Vesicular Acetylcholine Transporter Imaging Agents

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Ex vivo and in vivo evaluation of (2R,3R)‐5‐[¹⁸F]‐fluoroethoxy‐ and fluoropropoxy‐benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter

Ex vivo and in vivo evaluation of (2R,3R)‐5‐[¹⁸F]‐fluoroethoxy‐ and fluoropropoxy‐benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides