@article {Huang1033, author = {Ya-Yao Huang and Wen-Sheng Huang and Hung-Ming Wu and Yu -Yeh Kuo and Yu-Ning Chang and Pei-Yao Lin and Chi-Han Wu and Ruoh-Fang Yen and Chyng-Yann Shiue}, title = {Automated Production of [18F]FEPPA as a Neuroinflammation Imaging Agent}, volume = {57}, number = {supplement 2}, pages = {1033--1033}, year = {2016}, publisher = {Society of Nuclear Medicine}, abstract = {1033Objectives Neuroinflammation plays an important role in many neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson{\textquoteright}s disease, multiple sclerosis and Alzheimer{\textquoteright}s disease (1). Several PET tracers have been developed to monitor progression of neuroinflammation or measure therapeutic efficacy (2). Among those, [18F]FEPPA (2) has been found to be one of the potent neuroinflammation imaging agents (3). In order to fulfill the demand of this tracer for pre-clinical and clinical studies, we have developed an automated synthesis and simplified the purification procedure of 2. We report herein the automated synthesis of 2 and its application in neuroinflammation imaging.Methods 2 was synthesized manually and purified with 50:50 MeOH:H2O+0.5\% formic acid as HPLC mobile phase previously (4). We have synthesized this tracer with TRACERlab FXFN module and purified with 40\% EtOH as HPLC mobile phase. Briefly, fluorination of the tosylate precursor (1) with K[18F]/K2.2.2in anhydrous MeCN at 70 0C for 20 min gave the crude product. After dilution with H2O, the crude product was purified with a semi-preparative HPLC (Waters Xterra RP-18, 10⊆250mm, 40\% EtOH, 4 mL/min). The fraction containing 2 was collected, diluted with H2O and passed through a 0.22μm sterilizing filter into a sterile vial (Scheme 1). The neuroinflammation animal model was induced in male C57BL/6 mice. Mice (20-25 g, n=6) were intraperitoneally injected with a single dose of LPS (E. Coli 011:B4, 5 mg/kg). Twenty-four hours after LPS injection, mice were injected (i.v) with ~ 250 μCi of 2 and imaged with Argus PET/CT scanner. Dynamic sinograms were produced with 12 x10 sec, 3 x60 sec, 3 x 300 sec, 4 x 6000 sec, 2 x 900 sec frames. Averaged microPET images of the whole scan (90 min) were acquired using eXplore Vista PET-CT MMWKS software.Results The radiochemical yield of 2 synthesized by this method was 13{\textpm}8 \% (EOS, n=5) in a synthesis time of ~59 min from EOB. Radiochemical purity was \>95 \% with a specific activity of 34{\textpm}17 GBq/μmol (EOS, n=5). The EtOH content in 2 was \< 10\%. MicroPET images showed that LPS administration significantly increased mice brains uptake of 2 compared to normal mice (Fig. 1).Conclusions With this improved synthesis method, 2 has been produced in high quantities with good quality, and is ready for using in various clinical or pre-clinical studies. REFERENCES: 1. Heneka MT, Golenbock DT, Latz E. Innate immunity in Alzheimer{\textquoteright}s disease. Nat Immunol. 2015;16(3):229-236. 2. Ory D, Celen S, Verbruggen A, Bormans G, PET radioligands for in vivo visualization of neuroinflammation. Current Pharmaceutical Design, 2014, 20, 5897-913. 3. Wilson AA, Garcia A, Parkes J, et al. Radiosynthesis and initial evaluation of [18F]FEPPA for PET imaging of peripheral benzodiazepine receptors. Nucl Med Biol. 2008;35(3):305-314. 4. Suridjan I, Pollock B, Verhoeff N, et al. In-vivo imaging of grey and white matter neuroinflammation in Alzheimer{\textquoteright}s disease: a positron emission tomography study with a novel radioligand, [18F]FEPPA. Mol Psychiatry. 2015;20(12):1579-1587. $$graphic_5EC71BED-4590-485B-99EC-502829DBC4BC$$ $$graphic_75B56F70-F579-492E-AF7F-DA331164CDC0$$}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/57/supplement_2/1033}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }