英国牛津大学Gouverneur Vronique团队报道了[18F]二氟苯用于正电子发射层析成像。相关研究成果发表在2022年3月28日出版的国际学术期刊《自然》。
全身正电子发射断层扫描（PET）的出现极大地拓宽了这种强大的分子成像技术的研究和临床应用范围。这种可能性加速了18F放射化学的进展，有许多方法可用于18F标记（杂）芳烃和烷烃。然而，获得高摩尔活性（Am）的18F二氟甲基化分子在很大程度上是一个尚未解决的问题，尽管二氟甲基对于药物发现是不可或缺的。
该文中，研究人员报告了一种通用解决方案，即通过[18F]二氟卡宾试剂将卡宾化学引入核成像领域，该试剂能够进行多种18F二氟甲基化过程。与数十种已知的二氟卡宾试剂相比，这种18F试剂经过精心设计，易于使用，具有较高的摩尔活性和通用性。通过检测二氟卡宾前体电子变化时同位素稀释的可能性试验解决了Am的问题。多个基于[18F]二氟卡宾的反应，包括O–H、S–H和N–H插入，以及利用普遍存在的官能团（如（硫）酚、N-杂芳烃和易于安装的芳基硼酸）反应性的交叉偶联，证明了其多功能性。这种影响通过标记高度复杂和功能化的生物相关分子和放射性示踪剂来说明。
附：英文原文
Title: [18F]Difluorocarbene for Positron Emission Tomography
Author: Sap, Jeroen B. I., Meyer, Claudio F., Ford, Joseph, Straathof, Natan J. W., Drr, Alexander B., Lelos, Mariah J., Paisey, Stephen J., Mollner, Tim A., Hell, Sandrine M., Trabanco, Andrs A., Genicot, Christophe, am Ende, Christopher W., Paton, Robert S., Tredwell, Matthew, Gouverneur, Vronique
Issue&Volume: 2022-03-28
Abstract: The advent of total-body Positron Emission Tomography (PET) has vastly broadened the range of research and clinical applications of this powerful molecular imaging technology1. Such possibilities have accelerated progress in 18F-radiochemistry with numerous methods available to 18F-label (hetero)arenes and alkanes2. However, access to 18F-difluoromethylated molecules in high molar activity (Am) is largely an unsolved problem, despite the indispensability of the difluoromethyl group for pharmaceutical drug discovery3. We report herein a general solution by introducing carbene chemistry to the field of nuclear imaging with a [18F]difluorocarbene reagent capable of a myriad of 18F-difluoromethylation processes. In contrast to the tens of known difluorocarbene reagents, this 18F-reagent is carefully designed for facile accessibility, high molar activity and versatility. The issue of Am is solved using an assay examining the likelihood of isotopic dilution upon variation of the electronics of the difluorocarbene precursor. Versatility is demonstrated with multiple [18F]difluorocarbene based reactions including O–H, S–H and N–H insertions, and cross-couplings that harness the reactivity of ubiquitous functional groups such as (thio)phenols, N-heteroarenes, and aryl boronic acids that are easy to install. Impact is illustrated with the labelling of highly complex and functionalised biologically relevant molecules and radiotracers.
DOI: 10.1038/s41586-022-04669-2
Source: https://www.nature.com/articles/s41586-022-04669-2