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[18F]-GE-179 positron emission tomography (PET) tracer for N-methyl-d-aspartate receptors: One-pot synthesis and preliminary micro-PET study in a rat model of MCAO

Weiyan Zhou,Weiqi Bao,Donglang Jiang,Yanyan Kong,Fengchun Hua,Xiuhong Lu,Yihui Guan

Introduction The objective of this study was to synthesize an N -methyl- d -aspartate receptor (NMDAR) radiotracer [ 18 F]-GE-179 in one-pot and evaluate its in vivo binding for NMDAR activation after brain ischemia reperfusion injury. Methods [ 18 F]-GE-179 was auto-synthesized using a quick one-pot method from a stable disulfide precursor and purified using semi-preparative high-performance liquid chromatography (HPLC) with ethanol/aqueous NaH 2 PO 4 as the eluent. Dynamic micro-positron emission tomography (PET)/computed tomography (CT) study of [ 18 F]-GE-179 was successfully performed using a rat model of middle cerebral artery occlusion (MCAO, induced by transient occlusion into the left MCA). A simplified reference tissue model method was used to calculate the [ 18 F]-GE-179 non-displaceable binding potential (BPND) for intracranial NMDAR activation assessment. Immunofluorescence staining of NMDAR NR1 subunit in brain slices containing lesion was also performed. Results [ 18 F]-GE-179 was successfully prepared in a yield of 23–30% in a formulation that could be injected directly after dilution. Localized radioactivity accumulation was observed in the animal model of MCAO. Significantly higher ( p  = 0.0003–0.0404) BPND relative to equivalent contralateral was found in the ipsilateral caudate putamen , Acb core/shell, cortex cingulate , amygdala , hypothalamus , and superior colliculus . Immunofluorescence staining showed elevated NMDAR expression in the affected hemisphere. Conclusions [ 18 F]-GE-179 was synthesized using a one-pot process with a markedly improved yield. Preliminary in vivo micro-PET study visualized excessive NMDAR stimulation successfully in a rodent model of MCAO, which was consistent with results of in vitro immunofluorescence staining. The study demonstrates that [ 18 F]-GE-179 is a promising PET probe for the detection of functional NMDAR alterations.