A simple, rapid method for the preparation of [11C]formaldehyde
A simple, rapid method for the preparation of [11C]formaldehyde
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DOI：
10.1002/anie.200800991
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Fowler, Joanna S.
中科院分区：
文献类型：
--
作者：
Hooker, Jacob M.;Schoenberger, Matthias;Fowler, Joanna S.
碳-11与小分子的结合对于正电子发射断层扫描（PET）在体内分子成像和药物研发中的成功至关重要然而，使[11C]成为PET理想放射性核素的许多特性阻碍了它的化学发展。例如，半衰期短（t1/2= 20.4分钟），允许在短时间内重复研究，需要快速的化学合成和纯化。此外，高比活性提供了对低浓度受体和分子靶标成像的能力，使[11C]标记试剂的工作浓度范围在低纳摩尔范围内。但是，合成[11C]标记化合物的最大挑战可能是缺乏可用的标记试剂。请记住，几乎所有的碳-11合成都是从使用回旋加速器产生11CO2或11CH4的核反应[14N (p, α) 11C]开始的，必须从这些反应中制备标记试剂。到目前为止，用[11C]标记分子的最常见、最规范的方法是通过甲基化，通常是用11CH3I. b[2]虽然悬垂甲基经常出现在相关化合物中，[11C]-甲基化导致了许多成功的放射性示踪剂，但对甲基化的依赖限制了潜在探针的范围。因此，有必要开发新的反应，重点研究将[11C]结合到目标分子骨架位置的方法，一些研究小组已经开发或适应了将[11C]结合到苯环、碳环、杂环以及非悬垂位置的合成方法通过使用精心设计的有机反应，每一种都扩大了可获得的放射性示踪剂的类型。
The incorporation of carbon-11 into small molecules has been paramount to the success of positron emission tomography (PET) for in vivo molecular imaging and drug research and development.[1] However, many of the properties that make [11C] an ideal radionuclide for PET have impeded its chemical development. For instance, the short half-life (t1/2= 20.4 min), which allows for repeated studies within a short time span, necessitates rapid chemical syntheses and purifications. Moreover, high specific activity, which provides an ability to image low concentration receptors and molecular targets, places the working concentration range of [11C]-labeling reagents in the low nanomolar range. But perhaps the biggest challenge in the synthesis of [11C]-labeled compounds is the lack of available labeling reagents. Bear in mind, nearly all carbon-11 syntheses begin with a nuclear reaction [14N (p, α) 11C] using a cyclotron that produces 11CO2 or 11CH4 from which labeling reagents must be prepared.By far the most common, almost canonical method, to label a molecule with [11C] is through methylation, typically with 11CH3I.[2] While pendant methyl groups appear quite frequently in relevant compounds and [11C]-methylation has led to many successful radiotracers, reliance on methylation limits the range of potential probes. Consequently, there exists a need for new reaction development to focus on methods to incorporate [11C] in skeletal positions of target molecules and several research groups have developed or adapted synthetic methods for [11C]-incorporation into benzene rings, carbocycles, and heterocycles as well as non-pendant locations.[3] By using carefully designed organic reactions, each of these has expanded the types of radiotracers that can be accessed.