Abstract Transition‐metal mediated carbonylation with 11C‐labelled carbon monoxide ([11C]CO) is a versatile method for introducing 11C (t 1/2 = 20.3 min) into drugs and radioligands for subsequent use in positron emission tomography (PET). The aim of the current study was to perform the 11C‐carbonylation reaction on the interior surface of a stainless‐steel loop used for high performance liquid chromatography (HPLC). In the experimental setup, cyclotron produced 11C‐labelled carbon dioxide ([11C]CO2) was converted to [11C]CO by reduction over heated Molybdenum and swept into an HPLC loop pre‐charged with the appropriate reaction mixture. Following a 5 min reaction, the radiochemical purity (RCP) and the trapping efficiency (TE) of the reaction mixture was determined. After optimization, [11C]N‐Benzylbenzamide was obtained in quantitative radiochemical yield (RCY) following a 5 min reaction at room temperature. The methodology was further applied to label [11C]benzoic acid (RCP≥99%, TE>91%), [11C]methyl benzoate (RCP≥99%, TE>93%) and [11C]phthalide (RCP≥99%, TE>88%). A set of pharmaceuticals was finally radiolabelled using non‐optimized conditions. Excellent yields were obtained for the histamine‐3 receptor radioligand [11C]AZ13198083, the oncology drug [11C]olaparib and the dopamine D2 receptor radioligand [11C]raclopride, whereas a moderate yield was observed for the high‐affinity dopamine D2 receptor radioligand [11C]FLB457. The presented “in‐loop” process proved efficient for diverse 11C‐carbonylations, providing [11C]amides, [11C]esters and [11C]carboxylic acids in moderate to excellent RCYs. Based on the advantages associated with performing the radiolabelling step as an integrated part of the purification system, this methodology may become a valuable addition to the toolbox of methodologies used for 11C‐carbonylation of drugs and radioligands for PET.

中文翻译：

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“环内”羰基化——一种简化的药物和放射性配体碳 11 标记方法

摘要 过渡金属介导的 11C 标记的一氧化碳 ([11C]CO) 羰基化是一种将 11C (t 1/2 = 20.3 min) 引入药物和放射性配体以用于后续正电子发射断层扫描 (PET) 的通用方法。本研究的目的是在用于高效液相色谱 (HPLC) 的不锈钢环的内表面进行 11C 羰基化反应。在实验装置中，回旋加速器产生的 11C 标记的二氧化碳 ([11C]CO2) 通过在加热的钼上还原转化为 [11C]CO，并扫入预先装有适当反应混合物的 HPLC 回路。反应 5 分钟后，测定反应混合物的放射化学纯度 (RCP) 和捕集效率 (TE)。优化后，在室温下反应 5 分钟后，以定量放射化学产率 (RCY) 获得 [11C]N-苄基苯甲酰胺。该方法进一步应用于标记[11C]苯甲酸（RCP≥99%，TE>91%）、[11C]苯甲酸甲酯（RCP≥99%，TE>93%）和[11C]苯酞（RCP≥99%） , TE>88%)。一组药物最终使用非优化条件进行放射性标记。组胺-3 受体放射性配体 [11C]AZ13198083、肿瘤药物 [11C]olaparib 和多巴胺 D2 受体放射性配体 [11C] raclopride 获得了优异的产量，而高亲和力多巴胺 D2 受体放射性配体的产量中等。 11C]FLB457。所提出的“环内”过程被证明对不同的 11C 羰基化是有效的，在中等至优异的 RCY 中提供 [11C] 酰胺、[11C] 酯和 [11C] 羧酸。