Longitudinal PET Imaging of α7 Nicotinic Acetylcholine Receptors with [18F]ASEM in a Rat Model of Parkinson’s Disease

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Multi-Compartment SCFA Quantification in Human

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[ 18 F]‐labeled positron emission tomography ligand for the histamine H4 receptor

International audienceWe synthesized 5‐[ 18 F]‐fluoro‐1 H ‐indol‐2‐yl)(4‐methyl‐1‐piperazinyl)methanone ([ 18 F] 5 ) via a Suzuki approach starting from a protected pinacol borane precursor followed by acidic hydrolysis of the t ‐Boc protecting group. The non‐optimized radiochemical yield was 5.7 ± 1.35%, radiochemical purity was over 99%, and molar activity was 100.7 ± 34.5 GBq/μmol ( n = 3). [ 18 F] 5 was stable in rat plasma for at least 4 h and was evaluated by μPET imaging and biodistribution using a unilateral quinolinic acid rat model of neuroinflammation. The time‐activity curve showed that [ 18 F] 5 entered the brain immediately after intravenous injection and then left it progressively with a very low level reached from 30 min after injection. The biodistribution study showed no difference in the accumulation of [ 18 F] 5 between the lesioned and intact side of the brain and between control rats and animals pretreated with a saturating dose of JNJ‐7777120 as a specific H4R antagonist. Hence, despite its in vitro nanomolar affinity for H4R, and its ability to cross the blood–brain barrier in rats, [ 18 F] 5 does not appear suitable to image in vivo the receptor by PET

Design of α\alpha7 nicotinic acetylcholine receptor ligands in quinuclidine, tropane and quinazoline series. Chemistry, molecular modeling, radiochemistry, in vitro and in rats evaluations of a [18^{18}F] quinuclidine derivative

International audienceIn this report, we describe the synthesis of a novel library of $\alpha$7 nAChR ligands based on the modulationof the quinuclidine, quinazoline and tropane moieties. Spirane derivatives were newly synthesized understereo specific 1,3 dipolar cylcoadditions. Only amide derivatives bonded efficiently to the receptor withKi measured between 14 and 133 nM. The best fluorinated candidate was selected and radiolabeled. Thepotent [$^{18}$F]4 PET tracer was evaluated in rats and its brain accumulation quantified

Evaluation of the binding characteristics of [18F]FBVM in non-human primates a new radiotracer for imaging the vesicular acetylcholine transporter in vivo using positron emission tomography

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Extensive exploration of a novel rat model of Parkinson's disease using partial 6-hydroxydopamine lesion of dopaminergic neurons suggests new therapeutic approaches

International audienceParkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons constituting the nigrostriatal pathway. Neuroinflammation, related to microglial activation, plays an important role in this process. Exploration of animal models of PD using neuroimaging modalities allows to better understand the pathophysiology of the disease. Here, we fully explored a moderate lesion model in the rat in which 6-Synaps

Evaluation of the binding characteristics of [18F]FBVM in non-human primates a new radiotracer for imaging the vesicular acetylcholine transporter in vivo using positron emission tomography

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radiotracer for imaging the vesicular acetylcholine transporter in vivo using positron emission tomography

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radiotracer for imaging the vesicular acetylcholine transporter in vivo using positron emission tomography

International audienc

Development and preclinical evaluation of [18F]FBVM as a new potent PET tracer for vesicular acetylcholine transporter

International audienceAge-related neurodegenerative diseases have in common the occurrence of cognitive impairment, a highly incapacitating process that involves the cholinergic neurotransmission system. The vesicular acetylcholine transporter (VAChT) positron emission tomography (PET) tracer [18F]fluoroethoxybenzovesamicol ((−)-[18F]FEOBV) has recently demonstrated its high value to detect alterations of the cholinergic system in Alzheimer's disease, Parkinson's disease and dementia with Lewy body. We present here the development of the new vesamicol derivative tracer (−)-(R,R)-5-[18F]fluorobenzovesamicol ((−)[18F]FBVM) that we compared to (−)[18F]FEOBV in the same experimental conditions. We show that: i) in vitro affinity for the VAChT was 50-fold higher for (−)FBVM (Ki = 0.9 ± 0.3 nM) than for (−)FEOBV (Ki = 61 ± 2.8 nM); ii) in vivo in rats, a higher signal-to-noise specific brain uptake and a lower binding to plasma proteins and peripheral defluorination were obtained for (−)[18F]FBVM compared to (−)[18F]FEOBV. Our findings demonstrate that (−)[18F]FBVM is a highly promising PET imaging tracer which could be sufficiently sensitive to detect in humans the cholinergic denervation that occurs in brain areas having a low density of VAChT such as the cortex and hippocampus