Abnormally aggregated tau is the hallmark pathology of tauopathy neurodegenerative disorders and is a target for development of both diagnostic tools and therapeutic strategies across the tauopathy disease spectrum. Development of carbon-11- or fluorine-18-labeled radiotracers with appropriate affinity and specificity for tau would allow noninvasive quantification of tau burden using positron emission tomography (PET) imaging. We have synthesized [(18)F]lansoprazole, [(11)C]N-methyl lansoprazole, and [(18)F]N-methyl lansoprazole and identified them as high affinity radiotracers for tau with low to subnanomolar binding affinities. Herein, we report radiosyntheses and extensive preclinical evaluation with the aim of selecting a lead radiotracer for translation into human PET imaging trials. We demonstrate that [(18)F]N-methyl lansoprazole, on account of the favorable half-life of fluorine-18 and its rapid brain entry in nonhuman primates, favorable kinetics, low white matter binding, and selectivity for binding to tau over amyloid, is the lead compound for progression into clinical trials.

The field of radiochemistry is moving towards exclusive use of automated synthesis modules for production of clinical radiopharmaceutical doses. Such a move comes with many advantages, but also presents radiochemists with the challenge of re-configuring synthesis modules for production of radiopharmaceuticals that require non-conventional radiochemistry whilst maintaining full automation. This review showcases the versatility of the Tracerlab FXFN synthesis module by presenting simple, fully automated methods for producing [18F]FLT, [18F]FAZA, [18F]MPPF, [18F]FEOBV, [18F]sodium fluoride, [18F]fluorocholine and [18F]SFB.

The field of radiochemistry is moving toward exclusive use of automated synthesis modules for production of clinical radiopharmaceutical doses. Such a move not only comes with many advantages but also presents radiochemists with the challenge of re‐configuring synthesis modules for production of radiopharmaceuticals that require non‐conventional radiochemistry while maintaining full automation. Herein, we continue our series of articles showcasing the versatility of the Tracerlab FX synthesis modules by presenting straightforward, fully automated methods for preparing a range of carbon‐11 labeled radiopharmaceuticals using a Tracerlab FXC‐Pro. Strategies for production of [11C]acetate, [11C]carfentanil, [11C]choline, [11C]3‐amino‐4‐[2‐[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile ([11C]DASB), (+)‐a‐[11C]dihydroterabenazine ([11C]DTBZ), [11C]flumazenil ([11C]FMZ), meta‐hydroxyephedrine ([11C]HED), [11C]methionine, [11C]PBR28, [11C]Pittsburgh Compound B ([11C]PiB), 1‐[11C]methylpiperidin‐4‐yl propionate ([11C]PMP), and [11C]raclopride are presented. Copyright © 2011 John Wiley & Sons, Ltd.

Radiolytic decomposition of high specific concentration radiopharmaceuticals is an undesired side-effect that can hamper development of novel PET tracers. This was particularly evident in a series of carbon-11 and fluorine-18 labeled mono- and dimethyl-substituted aryl amines, where rapid decomposition was observed in isolation and formulation steps. We tested a number of additives that inhibit radiolysis and can be safely added to the synthesis procedures (purification and isolation) and reformulation steps to provide suitable clinical formulations. Ethanol and sodium ascorbate are established anti-oxidant stabilizers that completely inhibit radiolytic decomposition and are amenable to human use. Herein, we also demonstrate for the first time that nitrones are non-toxic radical scavengers that are capable of inhibiting radiolysis.

Introduction A novel one-pot method for preparing [18F]fluoromethylcholine ([18F]FCH) via in situ generation of [18F]fluoromethyl tosylate ([18F]FCH2OTs), and subsequent [18F]fluoromethylation of dimethylaminoethanol (DMAE), has been developed. Methods [18F]FCH was prepared using a GE TRACERlab FXFN, although the method should be readily adaptable to any other fluorine-18 synthesis module. Initially ditosylmethane was fluorinated to generate [18F]FCH2OTs. DMAE was then added and the reaction was heated at 120°C for 10 min to generate [18F]FCH. After this time, reaction solvent was evaporated, and the crude reaction mixture was purified by solid-phase extraction using C18-Plus and CM-Light Sep-Pak cartridges to provide [18F]FCH formulated in USP saline. The formulated product was passed through a 0.22 μm filter into a sterile dose vial, and submitted for quality control testing. Total synthesis time was 1.25 hours from end-of-bombardment. Results Typical non-decay-corrected yields of [18F]FCH prepared using this method were 91 mCi (7% non-decay corrected based upon ~1.3 Ci [18F]fluoride), and doses passed all other quality control (QC) tests. Conclusion A one-pot liquid-phase synthesis of [18F]FCH has been developed. Doses contain extremely low levels of residual DMAE (31.6 μg / 10 mL dose or ~3 ppm) and passed all other requisite QC testing, confirming their suitability for use in clinical imaging studies.