Characterization of the radiosynthesis and purification of [18F]THK-5351, a PET ligand for neurofibrillary tau

Abstract

This work characterizes the radiochemical synthesis, purification, and formulation of [18F]THK-5351, a tau PET radioligand, and develops an automated radiosynthesis routine (ELIXYS, Sofie Biosciences). Nucleophilic radiofluorination reaction was complete by 7 minutes at 110°C with radiochemical yields proportional to precursor mass (0.1–0.5 mg). Optimized HPLC purification produced radiotracer product with no chemical impurities observed on analytical HPLC in formulation. Automated radiosynthesis (ELIXYS), HPLC purification and formulation was completed in 86 minutes producing formulated product suitable for human research use.

In Vivo Characterization and Quantification of Neurofibrillary Tau PET Radioligand 18F-MK-6240 in Humans from Alzheimer Disease Dementia to Young Controls

“…18 F-MK-6240. 18 F-MK-6240 was synthesized in a manner similar to previously reported methods (18) with modifications to improve 18 F-MK-6240 radiochemical yield and automated using a Sofie ELIXYS (21) and a computer-controlled fraction collection, solidphase extraction, and formulation module previously validated for human use (22). 18 F-Fluoride was isolated from bulk target 18 O-water (98% enrichment) after cyclotron irradiation (;20 mAÁh) using an and underwent solid-phase extraction (tC18 Sep-Pak Plus Short, rinsed with 15 mL sterile water for injection, USP, eluted with 1 mL dehydrated ethanol).…”

Strategy for Screening of Antioxidant Compounds from Two Ulmaceae Species Based on Liquid Chromatography-Mass Spectrometry

“…The solid-phase extraction (SPE) procedure was performed using the modified method described previously by Hamedeyazdan et al (2017) [ 29 ] and Betthauser et al (2017) [ 30 ]. In this experiment, SPE was performed for 70% ethanol extracts (2 g) from A. aspera and Z. serrata leaves, and the quantified extracts were re-constituted in 70% ethanol (700 μL, 1,400,000 ppm).…”

The imaging features and clinical associations of a novel tau PET tracer - 18F-APN1607(18F-PM-PBB3) in Alzheimer’s disease

“…Over the last few years, several tau tracers have developed in the living human brain, including the first-generation tau trace such as 18 F-AV-1451 [6,7], 18 F-THK-5117, 18 F-THK-5317, and 18 F-THK-5351 [8][9][10][11], and the novel second-generation tau tracers, such as 11 C-PBB3, 18 F-RO69558948, 18 F-MK6240 and 18 F-PI2620 [12][13][14]. The first generation tau traces had several limitations, for example, 'off-target' binding; that is, the signal from tau tracers are due to monoamine oxidase B (MAO-B) binding [15].…”

“…PBB3 is a tau tracer developed in 2014. After preclinical evaluation, 11 C-PBB3 has been demonstrated to effectively visualize tau pathology in patients with AD and non-AD tauopathies [12,21]. Notably, the high-level retention of 11 C-PBB3 in the AD hippocampus, wherein tau pathology is enriched, sharply safety studies to ensure that they were medically stable after participating in this study.…”