[18F]Fluorination Optimisation and the Fully Automated Production of [18F]MEL050 Using a Microfluidic System

Abstract

The [ 18 F]radiolabelling of the melanin-targeting positron-emission tomography radiotracer [ 18 F]MEL050 was rapidly optimised using a commercial continuous-flow microfluidic system. The optimal [ 18 F]fluorination incorporation conditions were then translated to production-scale experiments (35-150 GBq) suitable for preclinical imaging, complete with automated HPLC-solid phase extraction purification and formulation. [ 18 F]MEL050 was obtained in 43 AE 10 % radiochemical yield in ,50 min.

A Fluorine‐18 Radiolabeling Method Enabled by Rhenium(I) Complexation Circumvents the Requirement of Anhydrous Conditions

“…Traditionally, to provide an anhydrous environment, the [ 18 F]fluoride in water is trapped on an anion‐exchange resin (thus also removing radioactive cationic impurities), eluted with a complexing agent in aqueous/organic solvent mixture, and azeotropically dried in a distillation vial. This azeotropic drying is an inefficient and time‐consuming process (>15 mins), during which period, radioactivity (≥10 %) is lost due to the radioactive decay of the fluorine‐18 isotope, as well as non‐specific adsorption of [ 18 F]fluoride to the surface of the distillation vial, leading to lower radiochemical yield (RCY) of the PET radiotracer …”

“…Scheme 1s hows the synthetic route used to synthesize the ligand( 3)a nd complex (5)p recursors, as well as the non-radioactives tandards 4 and 6. N-Oxidation of 1,10-phenanthroline allowed for selective chlorination in the 2-position by the Vilsmeierr eagent to afford 3.N ucleophilica romatic substitution with azeotropically dried fluoride, using 18-crown-6 as ap hase-transfer catalyst, then affordedt he novel 2-fluoro-1,10-phenanthroline ligand (4). Ligands 3 and 4 weret hen chelated to aR e I metal center to attain complexes 5 and 6,r espectively (see the Supporting Information, sections 1.1-1.5).…”

Microfluidic Radiosynthesis of the Muscarinic M2 Imaging Agent [18F]FP-TZTP

“…The EtOH was evaporated at 908C for 15 min, before the residue was reconstituted in 1 mL of 10 % ethanolic saline solution as described previously. [16,17] Under these conditions, [ 18 F]FP-TZTP was obtained in 26 AE 10 % RCY (n ¼ 15), with a molar activity of 182 AE 65 GBq mmol À1 at EOS. The entire radiosynthesis was completed in 49 AE 2 min and radiochemical purity was .99 %.…”

“…[15] This customised system has produced a range of 18 F-radiotracers including [ 18 F]CB102, [ 18 F]fluoroalkylcholines, [15] and [ 18 F]MEL050. [16] More recently, it was demonstrated that this system was capable of producing up to three different 18 F-radiotracers sequentially, using the same starting batch of [ 18 F]fluoride. [17] Herein, we discuss the first account of the microfluidic radiolabelling optimisation and production of the muscarinic M 2 imaging agent [ 18 F]FP-TZTP.…”

Fluorine Chemistry

“…Blanch and Wentrup (University of Queensland) describe an investigation into fluorinated carbene reactive intermediates [1] ; Read and co-workers (UNSW) report on the synthesis of novel fluorous surfactant molecules [2] ; Chebib (University of Sydney) and co-workers describe the receptor binding properties of shape-controlled fluorinated GABA analogues [3] ; Matesic and co-workers (Australian Nuclear Science and Technology Organisation) publish a microfluidic protocol for the automated production of 18 F-labelled compounds [4] ; Fraser and Easton (ANU) review the state-of-the-art in biosynthesis approaches to fluorinated peptides and proteins [5] ; Gardiner (CSIRO) reviews the production and commercial applications of fluoropolymers [6] ; Patel and Liu (Macquarie University) describe the synthesis and conformational analysis of fluorinated N-heterocycles [7] ; Harper and co-workers (UNSW) report on the outcomes of S N 2 reactions performed in fluorinated ionic liquid media [8] ; Kassiou and co-workers (University of Sydney) report on the clandestine production of fluorinated recreational drugs [9] ; Hunter and co-workers (UNSW) describe an investigation of fluorinated proline derivatives as enantioselective organocatalysts [10] ; and in an international contribution to this issue, O'Hagan and co-workers (University of St Andrews, UK) report on the fluorovinyl thioether functional group as a novel potential bioisostere of thioester enolates. [11] I sincerely thank all of the authors who have made such fine contributions to this Research Front, as well as the editorial and administrative staff of Aust.…”