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Relevant academic research and scientific papers

Deuterium-substituted 2-(2′-((dimethylamino)methyl)-4′-[18F](fluoropropoxy)phenylthio)benzenamine as a serotonin transporter imaging agent

Positron emission tomography imaging of serotonin transporter (SERT) is useful for studying brain diseases with altered serotonergic function. A deuterated imaging agent, ([18F]2-((2-((bis(methyl-d3)amino)methyl)-4-(3-fluoropropoxy-1,1,2,2,3,3-d6)phenyl)thio)aniline, [18F]D12FPBM, [18F]1), was prepared as a new chemical entity. The deuterated agent, 1, showed excellent binding affinity to SERT; Ki was 0.086 nM, comparable with the undeuterated FPBM. In vivo biodistribution studies in rats with [18F]1 showed good brain uptake (1.09% dose/g at 2?min post injection) and high specific uptake into the hypothalamus (HY) as compared with cerebellum (CB) (HY/CB?=?7.55 at 120?min), suggesting a specific localization to SERT binding sites. Regional brain distribution in rats provided clear indication that [18F]1 concentrated in the hypothalamus, hippocampus, and striatum, areas with a high SERT density. Results indicate that very little D to H substitution effect was found; [18F]FPBM and [18F]1 showed very similar SERT binding. [18F]1 might be an excellent candidate for SERT imaging.

RADIOLABELED CANNABINOID RECEPTOR 2 LIGAND

The present invention relates to a compound of formula (I) wherein R1, R2, and R3 are defined as in the description and in the claims. The compound of formula (I) can be used as a radiolabeled ligand.

PYRIDINE AND PYRAZINE DERIVATIVES AS PREFERENTIAL CANNABINOID 2 AGONISTS

The invention relates to a compound of formula (I), wherein A1, A2 and R1-R5 are as defined in the description and in the claims. The compound of formula (I) can be used as cannabinoid 2 preferential agonist.

VMAT2 imaging agent, D6-[18F]FP-(+)-DTBZ: Improved radiosynthesis, purification by solid-phase extraction and characterization

Objectives: Recently, a deuterated tracer, D6-[18F]FP-(+)-DTBZ, 9-O-hexadeutero-3-[18F]fluoropropoxyl-(+)-dihydrotetrabenazine ([18F]9), targeting vesicular monoamine transporter 2 (VMAT2) in the central nervous system, wa

Deuterated 18F-9-O-hexadeutero-3-fluoropropoxyl-(+)-dihydrotetrabenazine (D6-FP-(+)-DTBZ): A vesicular monoamine transporter 2 (VMAT2) imaging agent

Introduction Vesicular monoamine transporters 2 (VMAT2) in the brain serve as transporter for packaging monoamine in vesicles for normal CNS neurotransmission. Several VMAT2 imaging agents, [11C]-(+)-DTBZ, dihydrotetrabenazine and [18F]FP-(+)-DTBZ (9-O-fluoropropyl-(+)-dihydro tetrabenazine, a.k.a. [18F]AV-133), are useful for studying the changes in brain function related to monoamine transmission by in vivo imaging. Deuterated analogs have been reported targeting VMAT2 binding sites. Methods A novel deuterated [18F]9-O-hexaduterofluoropropyl-(+)-dihydrotetrabenazine, [18F]D6-FP-(+)-DTBZ, [18F]1, was prepared as a VMAT2 imaging agent. This 18F agent which targeted VMAT2 was evaluated by in vitro binding, in vivo biodistribution and microPET imaging studies in rodents. Results The one step radiolabeling reaction led to the desired [18F]D6-FP-(+)-DTBZ, [18F]1, which showed excellent binding affinity to VMAT2 (Ki = 0.32 ± 0.07 nM) comparable to that of FP-(+)-DTBZ (Ki = 0.33 ± 0.02 nM) using [18F]FP-(+)-DTBZ and rat striatum membrane homogenates. In vivo biodistribution in normal rats showed that 1, exhibited excellent brain uptake and comparable high ratio of striatum to cerebellum (target/background) ratio at 1 h after injection (ratio of 6.05 ± 0.43 vs 5.66 ± 0.72 for [18F]FP-(+)-DTBZ vs [18F]1, respectively). MicroPET imaging studies in rats further confirm that the striatum with high VMAT2 concentration was clearly delineated in normal rat brain after iv injection of [18F]1. We observed minor changes of metabolism in rat plasma between these two agents; however, the changes showed little effect on regional brain uptake and retention. Conclusions The results reported here lend support for using [18F]D6-FP-(+)-DTBZ, [18F]1, as in vivo PET imaging agent for VMAT2 binding in the brain.

NOVEL DEUTERIUM SUBSTITUTED POSITRON EMISSION TOMOGRAPHY (PET) IMAGING AGENTS AND THEIR PHARMACOLOGICAL APPLICATION

The present invention relates to deuterated compounds according to Formula I-A, Formula II-A, Formula II-D, and Formula III-A. These compounds can be used as PET imaging agents for evaluating Parkinson's Disease, Alzheimer Disease, and for determining specific serotonin reuptake inhibitor (SSRIi) activity for treatment of depression. The present invention also relates to pharmaceutical compositions comprising a pharmaceutical acceptable carrier and a compound of Formula I-A, Formulae II-A, Formula II-D, or Formula III-A, or a pharmaceutically acceptable salt thereof.