摘要：

1114Objectives: The strategy of late-stage [18F]fluorination of target molecules will simplify the tedious and time-consuming fluorine-18 radiopharmaceutical production process. PhenoFluor was reported to radio-fluorinate target molecules through a concerted nucleophilic aromatic substitution (CSNAr) reaction and could be used for labelling not only electron-poor but also electron-rich molecules. Here we validated the labelling protocol of 4-nitrophenol and paracetamol with fluorine-18 via the mediate of PhenoFluor, and, on the basis of this protocol, further explored the feasibility of late-stage [18F]fluorination of the model RGD-peptide. Methods: 4-nitrophenol and paracetamol reacted with PhenoFluor resulting in two intermediates. The solutions of intermediates were used to elute the 18F-fluoride - trapped on an anion exchange cartridge - and intermediates were heated for 20 min at 130°C. The resulting [18F]4-Fluoronitrobenzene and [18F]N-(4-fluorophenyl)acetamide were isolated via a HPLC purification step. A phenol-derivative of c(RGDfK)(Pbf, OtBu) was designed and synthesized using c(RGDfK) (Pbf, OtBu) reacting with p-Hydroxybenzoic acid. The synthesis and labelling of the RGD intermediate followed the above-mentioned protocol. The deprotection of protecting groups of [18F]F-RGD peptide were performed following a separation via a preparative HPLC system. The eluting efficiency of 18F-fluoride from cartridges and the labelling efficiency as well as isolation strategy of 18F-labelled molecules were evaluated. Results: Elution of 18F from the anion exchange cartridge could be achieved with 80% efficiency using the intermediates' solution of p-Hydroxybenzoic acid and paracetamol while elution efficiency decreased to less than 10% when using RGD intermediate solution. The radiolabelling yields of [18F]4-Fluoronitrobenzene and [18F]N-(4-fluorophenyl)acetamide achieved values higher than 90% and 45%, respectively, confirming the feasibility of the labelling protocol as well as the feasibility of labelling compounds having amide group based on PhenoFluor mediated [18F]fluorination. However, the radiolabelling of RGD peptides with 18F following the same protocol presents a disappointing result including poor elution efficient (<10%) as well as low radiolabelling yield (<8%) indicating the limitation of the protocol when applying it to radiolabelling peptides. Nevertheless the deprotection and HPLC purification procedure demonstrated the robustness and simplicity of the method. It also resulted in a high molar activity of radiolabelled compounds due to the significant difference of retention times between 18F-labelled compounds and cold precursors, intermediates as well as the leaving groups. Conclusions: The radiolabelling protocol based on PhenoFluor mediated [18F]fluorination demonstrated the feasibility of radiolabelling molecules having amide group and the operational simplicity. However, the results of labelling of RGD peptide showed the limitation of the protocol requiring further investigations in the future.

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