Radiofluorination process development and Tau protein imaging studies of [F-18]FEONM

A new naphthol derivative, [F-18]FEONM, has been designed to be a new Tau protein PET imaging molecule for detecting Tau tangle status of Alzheimer's disease in a transgenic mouse model. In order to synthesize this molecule, 2-acetyl-6-methoxynaphthalene was the starting compound and needed five steps preparation to bonding functional and leaving group for preparing the precursor. Radiofluorination on the precursor was carried out by a modified [F-18]FDG autosynthesizer. After half an hour processing, it yielded more than 99% chemical and radiochemical purity product at up to 60% yield. Radiofluorination kinetic study showing 80% [F-18]FEONM would be produced within the first 5 min. The radiofluorination gap function factor is 0.122 for 150 min reaction. Recovery yield of crude [F-18]FEONM could be up to 60% by semi-preparative HILIC HPLC column purification with 95% ethanol elution. Brain glioma tumor mice PET imaging were performed after tail vein injecting [F-18]FEONM. Binding in mice brain tumor reached steady state after 30 min injection and shows 30–70% higher uptake compared to normal mouse. The static brain tumor uptake showed the summation accumulation binding rate was 60% faster than normal mouse. In vitro postmortem AD patient brain slice binding showed 70% higher uptake than normal brain. The uptake of spherical stem cells also showed higher association with neuronal differentiation and PET imaging of Tau and ABeta transgenic mice also showed visualized difference. The specific binding ratio of hippocampus to cerebellum of control mouse is 46.56%, cortex to cerebellum is 11.08% in a 12-month-old P301S Tau transgenic mouse; hippocampus to cerebellum is 106.66%, cortex to cerebellum is 82.48%. Relative ratio of hippocampus to cerebellum of a P301S mouse to control mouse is 2.29, cortex to cerebellum is 7.44.