近日，美国辛辛那提大学Wei Liu团队研究了烷基亲电试剂与¹¹C或¹⁸F标记的氟仿的三氟甲基化PET应用。相关论文发表在2025年12月18日出版的《科学》杂志上。

正电子发射断层扫描（PET）示踪剂的持续发展对推动生物医学研究与临床诊断中的分子成像至关重要。长期以来，PET成像放射化学面临的一个突出局限是：尽管三氟甲基（CF₃）基团在生物活性分子和放射性药物中的应用日益广泛，但缺乏在C(sp³)位点进行放射性标记的通用方法。

研究组提出了一种在C(sp³)位点后期引入[¹⁸F]CF₃或[¹¹C]CF₃基团的通用策略。该方法分别基于卤原子转移和光氧化还原催化，通过独特的铜介导放射性三氟甲基化反应，实现了对烷基卤化物和烷基羧酸的高效标记。研究已成功对超过50种复杂分子及药物制剂进行了氟-18（¹⁸F）或碳-11（¹¹C）标记。通过此方法合成了两种备受期待的放射性配体——[¹⁸F]SL25.1188和[¹⁸F]PS13，它们作为其¹¹C对应物的长半衰期¹⁸F类似物，为人类PET成像展示了巨大应用潜力。

附：英文原文

Title: Trifluoromethylation of alkyl electrophiles with 11C- or 18F-labeled fluoroform for PET applications

Author: Chao Wang, Paul DeMent, Susovan Jana, Jinsoo Hong, Victor W. Pike, Wei Liu

Issue&Volume: 2025-12-18

Abstract: Continued development of positron emission tomography (PET) tracers is essential for advancing molecular imaging in biomedical research and clinical diagnostics. A long-standing limitation in radiochemistry for PET imaging has been the lack of general methods for radiolabeling trifluoromethyl (CF3) groups at C(sp3) sites, despite their growing prevalence in bioactive molecules and radiopharmaceuticals. Here, we present a general approach for late-stage installation of either a [18F]CF3 or [11C]CF3 group at a C(sp3) site. This method leverages unusual copper-mediated radiotrifluoromethylation of alkyl halides and alkyl carboxylic acids by halogen atom transfer and photoredox catalysis, respectively. More than 50 complex molecules and pharmaceutical agents were efficiently labeled with fluorine-18 (18F) or carbon-11 (11C). Two long-sought-after radioligands, [18F]SL25.1188 and [18F]PS13, were synthesized, providing longer-lived 18F analogs of their 11C counterparts with great promise for human PET imaging.

DOI: ady2969

Source: https://www.science.org/doi/10.1126/science.ady2969