Dahl Kenneth, Collier Thomas L, Cheng Ran, Zhang Xiaofei, Sadovski Oleg, Liang Steven H, Vasdev Neil
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, and Department of Radiology, Harvard Medical School, Boston, MA, USA.
Advion Inc, Ithaca, NY, USA.
J Labelled Comp Radiopharm. 2018 Mar;61(3):252-262. doi: 10.1002/jlcr.3528. Epub 2017 Jul 25.
Carbon-11-labeled carbon dioxide is the most common feedstock for the synthesis of positron emission tomography radiotracers and can be directly used for C-carbonylation. Herein, we report the development of an apparatus that takes advantage of "in-loop" technologies to facilitate robust and reproducible syntheses of C-carbonyl-based radiotracers by [ C]CO -fixation. Our "in-loop" [ C]CO -fixation method is simple, efficient, and proceeds smoothly at ambient pressure and temperature. We selected model C-carbonyl-labeled carbamates as well as symmetrical and unsymmetrical ureas based on their widespread use in radiotracer design and our clinical research interests for proof of concept. Utility of this method is demonstrated by the synthesis of a reversible radiopharmaceutical for monoamine oxidase B, [ C]SL25.1188, and 2 novel fatty acid amide hydrolase inhibitors. These radiotracers were isolated and formulated (>3.5 GBq; 100 mCi) with radiochemical purities (>99%) and molar radioactivity (≥80 GBq/μmol; ≥2162 mCi/μmol).
碳-11标记的二氧化碳是合成正电子发射断层扫描放射性示踪剂最常用的原料，可直接用于碳羰基化反应。在此，我们报告了一种利用“环内”技术开发的装置，该装置通过[¹¹C]CO₂固定来促进基于¹¹C-羰基的放射性示踪剂的稳健且可重复的合成。我们的“环内”[¹¹C]CO₂固定方法简单、高效，并且在常压和常温下顺利进行。基于它们在放射性示踪剂设计中的广泛应用以及我们的临床研究兴趣，我们选择了¹¹C-羰基标记的氨基甲酸酯模型以及对称和不对称脲作为概念验证。通过合成一种用于单胺氧化酶B的可逆放射性药物[¹¹C]SL25.1188以及两种新型脂肪酸酰胺水解酶抑制剂，证明了该方法的实用性。这些放射性示踪剂被分离并配制（>3.5 GBq；100 mCi），放射化学纯度（>99%）和摩尔放射性（≥80 GBq/μmol；≥2162 mCi/μmol）。
