Ascertaining the Suitability of Aryl Sulfonyl Fluorides for [¹⁸F]Radiochemistry Applications: A Systematic Investigation using Microfluidics

Abstract

Optimization of [(18)F]radiolabeling conditions and subsequent stability analysis in mobile phase, PBS buffer, and rat serum of 12 aryl sulfonyl chloride precursors with various substituents (electron-withdrawing groups, electron-donating groups, increased steric bulk, heterocyclic) were performed using an Advion NanoTek Microfluidic Synthesis System. A comparison of radiochemical yields and reaction times for a microfluidics device versus a conventional reaction vessel is reported. [(18)F]Radiolabeling of sulfonyl chlorides in the presence of competing nucleophiles, H-bond donors, and water was also assessed and demonstrated the versatility and potential utility of [(18)F]sulfonyl fluorides as synthons for indirect radiolabeling.

Tolerance of Water in Microfluidic Radiofluorinations: A Potential Methodological Shift?

“…In both examples, we obtained maximum isolated yields of >80%. The case of 9-Cl was particularly noteworthy since radiolabeling conducted using anhydrous conditions demonstrated that the fluorination reaction can occur only at low temperatures and with a higher concentration of precursor (>2 mg/mL), probably due to competing decomposition of the acid [16]. Instead, in the presence of the hydrous complex (5% H 2 O), a low concentration (0.5 mg/mL) of 9-Cl was sufficient to obtain 91% radiochemical incorporation yield at 30°C at a flow rate of 20 μL/min for both precursor and fluorination complex.…”

Magnetic Droplet Microfluidics as a Platform for the Concentration of [18F]Fluoride and Radiosynthesis of Sulfonyl [18F]Fluoride

“…1 This procedure requires positron-emitting biomolecules that selectively bind to the biological area of interest (i.e., cellular targets or receptors). The radioisotope 18 F is often considered to be the best positron-emitter, owing to its appropriate decay half-life (109.7 min), which balances patient dose with pharmacokinetic clearance of the tracer itself. The half-life is also long enough to allow time for synthesis of radiotracers without much decay loss, and hence, 18 F can be manufactured commercially at offsite locations then shipped to PET centers.…”

“…Generally, the synthesis involves several procedural steps. The first step is the generation of the radioisotope [ 18 F]fluoride, which is produced by the proton bombardment of the target material (heavy oxygen water or H 2 18 O)), and the radionuclide is released from the cyclotron in the form of [ 18 2), or a large organic counterion, e.g. tetrabutyl ammonium bicarbonate.…”

“…These particles are used to preconcentrate the [ 18 F]fluoride ion in the H 2 18 O liquid droplet. [ 18 F]fluoride ions are then released, and are used to synthesize a prosthetic compound which can subsequently be used to label a biomolecule (e.g., peptide) for PET.…”

“…These particles were adhered to a disc-shaped carrier magnet so that they were moved as a group on the Teflon sheet. In step 2, the magnetic particles were pulled toward the [ 18 F]fluoride/ H 2 18 O droplet, controlled via the magnet on the robotic arm. The magnetic particles were looped around the droplet to induce a stirring effect.…”