Abstract
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Background: It has been confirmed that α7-nicotinic acetylcholine receptor (α7nAChR) is an important target for early identification of atherosclerotic plaques. Previously, we have successfully designed and synthesized a series of 18F-labeled PET molecular probes targeting α7nAChR for the diagnosis of brain diseases. According to the characteristics of intravascular α7nAChR, a novel oxazolo [4,5-b] pyridine derivative was screened, synthesized and labeled with 18F nuclide. Later, we will use the novel synthesized molecular probe for α7nAChR binding experiments in vitro and dynamic micro PET-CT imaging of atherosclerosis New Zealand white rabbits. Meanwhile, it will be compared with the gold standard pathological examination of atherosclerosis to verify its reliability in the early diagnosis of atherosclerosis.
Methods: By means of molecular docking method, we designed and screened a novel ligand compound of 1.4 oxazolo [4,5-b] pyridine derivative, and calculated its lipid water distribution coefficient (logP). According to the design results, the compound was chemical synthesized and labeled with 18F radionuclide and 19F nuclide (Fig. 1). we also established the atherosclerotic plaques model of New Zealand white rabbits (Fig. 2). Results: The novel 1.4 oxazolo [4,5-b] pyridine derivative was successfully synthesized and its logP value was 1.88. In addition, the labeled precursor was automatically 18F-labeled using a Stynthra RNplus module. The radiochemical purity of the radioligand is more than 99%, and the radiolabeling rate is about 13.2% (without decay correction) Conclusion: We successfully synthesized a 18F-labeled oxazolo [4,5-b] pyridine derivative (logP =1.88) targeted to α7nAChR located in vessels. The atherosclerotic plaques model of New Zealand white rabbits were also successfully established Key words: Chemical synthesis; α7-nicotinic acetylcholine receptor(α7nAChR,); New Zealand white rabbits; 18F-labeled