Service de Chimie Bio-organique et Marquage, DMTS, Université Paris-Saclay, CEA, F-91191 Gif-sur-Yvette, France.
Laboratoire d'Imagerie Biomédicale Multimodale Paris-Saclay (BioMaps), Université Paris-Saclay, Inserm, CNRS, CEA, F-91401 Orsay, France.
J Am Chem Soc. 2023 Aug 2;145(30):16760-16770. doi: 10.1021/jacs.3c04679. Epub 2023 Jul 24.
The need for carbon-labeled radiotracers is increasingly higher in drug discovery and development (carbon-14, β, = 5730 years) as well as in positron emission tomography (PET) for in vivo molecular imaging applications (carbon-11, β, = 20.4 min). However, the structural diversity of radiotracers is still systematically driven by the narrow available labeled sources and methodologies. In this context, the emergence of carbon dioxide radical anion chemistry might set forth potential unexplored opportunities. Based on a dynamic isotopic equilibration between formate salts and [C, C, C]CO, C-labeled radical anion CO could be accessed under extremely mild conditions within seconds. This methodology was successfully applied to hydrocarboxylation and dicarboxylation reactions in late-stage carbon isotope labeling of pharmaceutically relevant compounds. The relevance of the method in applied radiochemistry was showcased by the whole-body PET biodistribution profile of [C]oxaprozin in mice.
在药物发现和开发（碳-14，β，半衰期=5730 年）以及正电子发射断层扫描（PET）的体内分子成像应用中（碳-11，β，半衰期=20.4 分钟），对碳标记放射性示踪剂的需求日益增加。然而，放射性示踪剂的结构多样性仍然受到可用标记源和方法的限制。在这种情况下，二氧化碳自由基阴离子化学的出现可能带来潜在的尚未开发的机会。基于甲酸盐盐和[C，C，C]CO 之间的动态同位素平衡，可以在几秒钟内，在极其温和的条件下获得 C 标记的自由基阴离子 CO。该方法成功地应用于药物相关化合物的后期碳同位素标记的氢羧化和二羧化反应。该方法在应用放射化学中的相关性通过 [C]oxaprozin 在小鼠体内的全身 PET 生物分布曲线得到了展示。
