Dahl Kenneth, Halldin Christer, Schou Magnus
Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Hospital, Karolinska Institutet, 171 76 Stockholm, Sweden.
Department of Clinical Neuroscience, AstraZeneca Translational Science Centre, Karolinska Institutet, 171 76 Stockholm, Sweden.
Clin Transl Imaging. 2017;5(3):275-289. doi: 10.1007/s40336-017-0223-1. Epub 2017 Feb 25.
This short review aims to cover the more recent and promising developments of carbon-11 (C) labeling radiochemistry and its utility in the production of novel radiopharmaceuticals, with special emphasis on methods that have the greatest potential to be translated for clinical positron emission tomography (PET) imaging.
A survey of the literature was undertaken to identify articles focusing on methodological development in C chemistry and their use within novel radiopharmaceutical preparation. However, since C-labeling chemistry is such a narrow field of research, no systematic literature search was therefore feasible. The survey was further restricted to a specific timeframe (2000-2016) and articles in English.
From the literature, it is clear that the majority of C-labeled radiopharmaceuticals prepared for clinical PET studies have been radiolabeled using the standard heteroatom methylation reaction. However, a number of methodologies have been developed in recent years, both from a technical and chemical point of view. Amongst these, two protocols may have the greatest potential to be widely adapted for the preparation of C-radiopharmaceuticals in a clinical setting. First, a novel method for the direct formation of C-labeled carbonyl groups, where organic bases are utilized as [C]carbon dioxide-fixation agents. The second method of clinical importance is a low-pressure C-carbonylation technique that utilizes solvable xenon gas to effectively transfer and react [C]carbon monoxide in a sealed reaction vessel. Both methods appear to be general and provide simple paths to C-labeled products.
Radiochemistry is the foundation of PET imaging which relies on the administration of a radiopharmaceutical. The demand for new radiopharmaceuticals for clinical PET imaging is increasing, and C-radiopharmaceuticals are especially important within clinical research and drug development. This review gives a comprehensive overview of the most noteworthy C-labeling methods with clinical relevance to the field of PET radiochemistry.
本简要综述旨在涵盖碳-11（C）标记放射化学的最新且有前景的进展及其在新型放射性药物生产中的应用，特别强调最有潜力转化用于临床正电子发射断层扫描（PET）成像的方法。
进行文献调研以确定关注C化学方法学发展及其在新型放射性药物制备中应用的文章。然而，由于C标记化学是一个如此狭窄的研究领域，因此无法进行系统的文献检索。该调研进一步限定在特定时间范围（2000 - 2016年）且为英文文章。
从文献中可知，为临床PET研究制备的大多数C标记放射性药物是使用标准杂原子甲基化反应进行放射性标记的。然而，近年来从技术和化学角度都开发了一些方法。其中，有两种方案可能最有潜力在临床环境中广泛应用于制备C放射性药物。第一种是直接形成C标记羰基的新方法，其中有机碱用作[C]二氧化碳固定剂。第二种具有临床重要性的方法是低压C羰基化技术，该技术利用可溶解的氙气在密封反应容器中有效转移和反应[C]一氧化碳。这两种方法似乎都具有通用性，并为制备C标记产物提供了简单途径。
放射化学是PET成像的基础，PET成像依赖于放射性药物的给药。临床PET成像对新放射性药物的需求在增加，C放射性药物在临床研究和药物开发中尤其重要。本综述全面概述了与PET放射化学领域临床相关的最值得注意的C标记方法。
