DESI-TQ-MS imaging for ex vivo brain biodistribution assessment: evaluation of LBT-999, a ligand of the dopamine transporter (DAT).

Background: Selection of the most promising radiotracer candidates for radiolabeling is a difficult step in the development of radiotracer pharmaceuticals, especially for the brain. Mass spectrometry (MS) is an alternative to study ex vivo the characteristics of candidates, but most MS studies are complicated by the pharmacologic doses injected and the dissection of regions to study candidate biodistribution. In this study, we tested the ability of a triple quadrupole analyzer (TQ LC-MS/MS) to quantify low concentrations of a validated precursor of a radiotracer targeting the DAT (LBT-999) in dissected regions.

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

Age-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 [F]fluoroethoxybenzovesamicol ((-)-[F]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-[F]fluorobenzovesamicol ((-)[F]FBVM) that we compared to (-)[F]FEOBV in the same experimental conditions.

[ F]-labeled positron emission tomography ligand for the histamine H4 receptor.

We synthesized 5-[ F]-fluoro-1H-indol-2-yl)(4-methyl-1-piperazinyl)methanone ([ 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.

Study of influence of the glutamatergic concentration of [F]FPEB binding to metabotropic glutamate receptor subtype 5 with N-acetylcysteine challenge in rats and SRM/PET study in human healthy volunteers.

Altered glutamate signaling is thought to be involved in a myriad of psychiatric disorders. Positron emission tomography (PET) imaging with [F]FPEB allows assessing dynamic changes in metabotropic glutamate receptor 5 (mGluR5) availability underlying neuropathological conditions. The influence of endogenous glutamatergic levels into receptor binding has not been well established yet.

Fully automated radiosynthesis of [F]LBT999 on TRACERlab FX and AllinOne modules, a PET radiopharmaceutical for imaging the dopamine transporter in human brain.

Background: Fluorine labelled 8-((E)-4-fluoro-but-2-enyl)-3β-p-tolyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid methyl ester ([F]LBT999) is a selective radioligand for the in vivo neuroimaging and quantification of the dopamine transporter by Positron Emission Tomography (PET).

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

Purpose: The nicotinic acetylcholine alpha-7 receptors (α7R) are involved in a number of neuropsychiatric and neurodegenerative brain disorders such as Parkinson's disease (PD). However, their specific pathophysiologic roles are still unclear. In this context, we studied the evolution of these receptors in vivo by positron emission tomography (PET) imaging using the recently developed tracer 3-(1,4-diazabicyclo[3.

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

Parkinson'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.

Design of α7 nicotinic acetylcholine receptor ligands in quinuclidine, tropane and quinazoline series. Chemistry, molecular modeling, radiochemistry, in vitro and in rats evaluations of a [(18)F] quinuclidine derivative.

In this report, we describe the synthesis of a novel library of α7 nAChR ligands based on the modulation of the quinuclidine, quinazoline and tropane moieties. Spirane derivatives were newly synthesized under stereo specific 1,3 dipolar cylcoadditions. Only amide derivatives bonded efficiently to the receptor with Ki measured between 14 and 133 nM.