A perspective on automated advanced continuous flow manufacturing units for the upgrading of biobased chemicals toward pharmaceuticals.

Biomass is a renewable, almost infinite reservoir of a large diversity of highly functionalized chemicals. The conversion of biomass toward biobased platform molecules through biorefineries generally still lacks economic viability. Profitability could be enhanced through the development of new market opportunities for these biobased platform chemicals. The fine chemical industry, and more specifically the manufacturing of pharmaceuticals is one of the sectors bearing significant potential for these biobased building blocks to rapidly emerge and make a difference. There are, however, still many challenges to be dealt with before this market can thrive. Continuous flow technology and its integration for the upgrading of biobased platform molecules for the manufacturing of pharmaceuticals is foreseen as a game-changer. This perspective reflects on the main challenges relative to chemical, process, regulatory and supply chain-related burdens still to be addressed. The implementation of integrated continuous flow processes and their automation into modular units will help for tackling with these challenges.

Automated radiosynthesis of the Pittsburg compound-B using a commercial synthesizer.

BACKGROUND: The Pittsburgh compound-B ([11C]PIB) is a highly interesting radiotracer for imaging amyloid plaques in Alzheimer's disease by positron emission tomography (PET). An increasing number of PET centres schedule its transfer for clinical studies and therefore are interested in its automated synthesis. METHOD: With the aim of flexibility, we reported the first fully automated synthesis of [11C]PIB with the coupling of two commercial synthesizers. RESULTS: [11C]PIB was prepared from 2-(4'-aminophenyl)-6-hydroxybenzothiazole by [11C]methyl triflate methylation reacting in an high-performance liquid chromatography loop and resulting in a total radiochemical yield of 13+/-15% after a synthesis time of 25 min. The specific activity of [11C]PIB was 20-60 GBq/micromol and its radiochemical purity is more than 99%. CONCLUSION: The rapid synthesis and the automatic auto-cleaning procedure allow convenient and reproducible [11C]PIB synthesis to be performed during the same day for preclinical or clinical PET scans.

Fully automated [18F]fluorocholine synthesis in the TracerLab MX FDG Coincidence synthesizer.

INTRODUCTION: We developed a new fully automated method for the radiosynthesis of [18F]fluorocholine by modifying the commercial 2-[18F]fluoro-2-d-deoxy-glucose ([18F]FDG) synthesizer module (GE TracerLab MX, formerly Coincidence). METHODS: [18F]Flurocholine was synthesized by (18)F-fluoroalkylation of N,N-dimethylaminoethanol using [18F]fluorobromomethane as fluoromethylating agent. [18F]Fluorobromomethane was produced by reaction of dibromomethane with [18F]fluoride, assisted by Kryptofix 2.2.2. RESULTS: After purification on solid-phase extraction cartridges, the [18F]fluorocholine was obtained in 15-25% radiochemical yields (decay not corrected), with more than 99% radiochemical purity. Specific activity was more than 37 GBq/micromol. Synthesis time was less than 35 min. CONCLUSION: This new automated synthesis technique provides high and reproducible yields that could be dedicated for routine use with the same [18F]FDG disposable cassette system.