Preserved Serotonin Transporter Availability in Parkinson Disease Measured with Either [C]MADAM or [C]DASB: A Study Including 2 Separate Cohorts of Nondepressed Patients.

Serotonin transporter (SERT) availability was assessed using 2 tracers, [C],-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ([C]DASB) and [C],-dimethyl-2-(2-amino-4-fluoromethylphenylthio)benzylamine) ([C]MADAM), in independent cohorts of patients and controls. This study aimed to independently confirm whether SERT remains intact in nondepressed individuals with early-stage Parkinson disease (PD), because the use of diverse methodologies could potentially yield disparate results. Seventeen PD patients (5 women and 12 men; age, 64 ± 7 y; Unified Parkinson's Disease Rating Scale motor score, 23 ± 5; Beck Depression Inventory score, 5 ± 4) and 20 age- and sex-matched healthy controls underwent [C]MADAM PET at Karolinska Institutet.

Identification and In Vitro and In Vivo Characterization of KAC-50.1 as a Potential α-Synuclein PET Radioligand.

The accumulation of aggregated α-synuclein (α-syn) is a pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. Here within, we report the in vitro characterization targeting site 2 of α-syn fibrils and in vivo evaluation of NHPs of KAC-50.1 as a potential α-syn positron emission tomography (PET) radioligand.

Exploring the Interactions between two Ligands, UCB-J and UCB-F, and Synaptic Vesicle Glycoprotein 2 Isoforms.

modeling was applied to study the efficiency of two ligands, namely, and , to bind to isoforms of the synaptic vesicle glycoprotein 2 (SV2) that are involved in the regulation of synaptic function in the nerve terminals, with the ultimate goal to understand the selectivity of the interaction between and to different isoforms of SV2. Docking and large-scale molecular dynamics simulations were carried out to unravel various binding patterns, types of interactions, and binding free energies, covering hydrogen bonding and nonspecific hydrophobic interactions, water bridge, π-π, and cation-π interactions. The overall preference for bonding types of and with particular residues in the protein pockets can be disclosed in detail.

Microsome Mediated in Vitro Metabolism: A Convenient Method for the Preparation of the PET Radioligand Metabolite [F]FE-PE2I-OH for Translational Dopamine Transporter Imaging.

Undesired radiometabolites can be detrimental to the development of positron emission tomography (PET) radioligands. Methods for quantifying radioligand metabolites in brain tissue include ex vivo studies in small animals or labeling and imaging of the radiometabolite(s) of interest. The latter is a time- and resource-demanding process, which often includes multistep organic synthesis.