Microwave-assisted radiosynthesis of [¹⁸F]ASEM, a radiolabeledα7-nicotinic acetylcholine receptor antagonist

Abstract

An improvement of the original radiochemical synthesis of [(18) F]ASEM, an α7-nicotinic acetylcholinergic receptor radioligand, is reported. The new procedure utilizes microwave-assisted radiofluorination. In addition, a new preparative HPLC method was developed to eliminate a chemical impurity in the final product. Quality control procedures were also enhanced to improve detection of product with enhanced resolution of potential impurities. [(18) F]ASEM was produced in 20.1 ± 8.9% non-decay corrected (NDC) yield with an average synthesis time of 57 min and an average specific radioactivity of 856 ± 332 GBq/µmol (23 ± 9 Ci/µmol).

An improved synthesis of the radiolabeled prostate-specific membrane antigen inhibitor, [18F]DCFPyL

“…With a radiofluorination synthesis of [ 18 F]DCFPyL that was similar in many ways to some of the standard [ 18 F]‐labeled radiotracers previously synthesized (ie, drying radioactive fluoride ion, reaction with an appropriate precursor, deprotection, and some method of purification; like [ 18 F]FDG or [ 18 F]FMISO), we turned our attention to appropriate platforms for performing the synthesis under automation. The in‐house, custom‐made RFM (a thermal heating adaptation of the microwave synthesis module described previously for making the α7‐nicotinergic ligand, [ 18 F]ASEM at high specific activity) was constructed. The RFM was built with components (valves, tubings, etc) that were free of fluorine in their manufacturing to minimize any fluorine contamination in the synthesis and designed to have fluid pathways that minimize transfer losses and transfer times from upright‐positioned, small‐volume reagent vessels.…”

Development of [ 18 F]ASEM, a specific radiotracer for quantification of the α7-nAChR with positron-emission tomography

“…With increased demand for the [ 18 F]ASEM for human and animal PET studies, a fast microwave-assisted synthesis with improved radiochemical yield (25-50%) was further developed[64]. The microwave method allows a routine preparation of about 500 mCi [ 18 F]ASEM per batch with high specific radioactivity (>10000 mCi/µmol) and radiochemical purity (>98%), which means that it can be used for several PET scans within the same day.…”

Synthesis and quality control of [18F]T807 for tau PET imaging

“…Using typical radiosyntheses involving [ 18 F]fluoride as a model, a simple semi-automated procedure outlined in Figure 1 for [ 18 F] T807 was devised using the microwave radiosynthesis module. 8,9 Briefly, [ 18 F]fluoride was trapped on a QMA cartridge, eluted from that cartridge with an aqueous solution of potassium carbonate (K 2 CO 3 ) and Kryptofix [2.2.2] in acetonitrile, and azeotropically dried with heating and additional acetonitrile. An acetonitrile solution of the t-BOC protected, trimethylammonium T807 precursor was added to the reaction vial and the vial was microwave irradiated to produce the [ 18 F]-labeled t-BOC protected T807.…”

“…Using typical radiosyntheses involving [ 18 F]fluoride as a model, a simple semi‐automated procedure outlined in Figure for [ 18 F]T807 was devised using the microwave radiosynthesis module . Briefly, [ 18 F]fluoride was trapped on a QMA cartridge, eluted from that cartridge with an aqueous solution of potassium carbonate (K 2 CO 3 ) and Kryptofix [2.2.2] in acetonitrile, and azeotropically dried with heating and additional acetonitrile.…”