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Abstract Background [13N]Ammonia is a cyclotron produced myocardial perfusion imaging agent. With the development of high-yielding [13N]ammonia cyclotron targets using a solution of 5 mM ethanol in water, there was a need to develop and validate an automated purification and formulation system for [13N]ammonia to be in a physiological compatible formulation of 0.9% sodium chloride since there is no widely available commercial system at this time. Due to its short half-life of 10 min, FDA and USP regulations allow [13N]ammonia to be tested in quality control (QC) sub-batches with limited quality control testing performed on the sub-batches for patient use. The current EP and the original USP method for the determination of the radiochemical purity and identity of [13N]ammonia depended on an HPLC method using a conductivity detector and a solvent free of other salts. This HPLC method created issues in a modern cGMP high volume PET manufacturing facility where the HPLC is used with salt containing mobile phase buffers for quality control analysis of other PET radiopharmaceuticals. Flushing of the HPLC system of residual salt buffers which may interfere with the [13N]ammonia assay can take several hours of instrument time. Since there are no mass limits on [13N]ammonia, a simplified TLC assay to determine radiochemical identity and purity could be developed to simplify and streamline QC. Results We have developed and validated a streamlined automated synthesis for [13N]ammonia which provides the drug product in 8 mL of 0.9% sodium chloride for injection. A novel radio-TLC method was developed and validated to demonstrate feasibility to quantitate [13N]ammonia and separate it from all known radiochemical impurities. Conclusions The process for automated synthesis of [13N]ammonia simplifies and automates the purification and formulation of [13N]ammonia in a cGMP compliant manner needed for high-throughput manufacture of [13N]ammonia. The novel radio-TLC method has simplified [13N]ammonia quality control (QC) and now enables it to be tested using the same QC equipment as [18F]fludeoxyglucose (FDA/USP recognized name for 2-[18F]fluoro-2-deoxy-D-glucose). Both the streamlined automated synthesis of [13N]ammonia and the novel radio-TLC method have been accepted and approved by the US Food and Drug Administration (FDA) for the cGMP manufacture of [13N]ammonia.

Despite extensive preclinical imaging with radiotracers developed by continuous-flow microfluidics, a positron emission tomographic (PET) radiopharmaceutical has not been reported for human imaging studies by this technology. The goal of this study was to validate the synthesis of the tau radiopharmaceutical 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole ([ 18 F]T807) and perform first-in-human PET scanning enabled by microfluidic flow chemistry. [ 18 F]T807 was synthesized by our modified one-step method and adapted to suit a commercial microfluidic flow chemistry module. For this proof of concept, the flow system was integrated to a GE Tracerlab FX FN unit for high-performance liquid chromatography purification and formulation. Three consecutive productions of [ 18 F]T807 were conducted to validate this radiopharmaceutical. Uncorrected radiochemical yields of 17 ± 1% of crude [ 18 F]T807 (≈ 500 mCi, radiochemical purity 95%) were obtained from the microfluidic device. The crude material was then purified, and > 100 mCi of the final product was obtained in an overall uncorrected radiochemical yield of 5 ± 1% ( n = 3), relative to starting [ 18 F]fluoride (end of bombardment), with high radiochemical purity (≥ 99%) and high specific activities (6 Ci/μmol) in 100 minutes. A clinical research study was carried out with [ 18 F]T807, representing the first reported human imaging study with a radiopharmaceutical prepared by this technology.