Rotstein Benjamin H, Hooker Jacob M, Woo Jiyeon, Collier Thomas Lee, Brady Thomas J, Liang Steven H, Vasdev Neil
Division of Nuclear Medicine and Molecular Imaging & Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital , Boston, Massachusetts 02114, United States ; Department of Radiology, Harvard Medical School , Boston, Massachusetts 02114, United States.
Department of Radiology, Harvard Medical School , Boston, Massachusetts 02114, United States ; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital , Charlestown, Massachusetts 02129, United States.
ACS Med Chem Lett. 2014 Feb 27;5(6):668-72. doi: 10.1021/ml500065q. eCollection 2014 Jun 12.
Bexarotene (Targretin) is a retinoid X receptor (RXR) agonist that has applications for treatment of T cell lymphoma and proposed mechanisms of action in Alzheimer's disease that have been the subject of recent controversy. Carbon-11 labeled bexarotene ([(11)C-carbonyl]4-[1-(3,5,5,8,8-pentamethyltetralin-2-yl)ethenyl]benzoic acid) was synthesized using a Cu-mediated cross-coupling reaction employing an arylboronate precursor 1 and [(11)C]carbon dioxide under atmospheric pressure in 15 ± 2% uncorrected radiochemical yield (n = 3), based on [(11)C]CO2. Judicious choice of solvents, catalysts, and additives, as well as precursor concentration and purity of [(11)C]CO2, enabled the preparation of this (11)C-labeled carboxylic acid. Formulated [(11)C]bexarotene was isolated (>37 mCi) with >99% radiochemical purity in 32 min. Preliminary positron emission tomography-magnetic resonance imaging revealed rapid brain uptake in nonhuman primate in the first 75 s following intravenous administration of the radiotracer (specific activity >0.3 Ci/μmol at time of injection), followed by slow clearance (Δ = -43%) over 60 min. Modest uptake (SUVmax = 0.8) was observed in whole brain and regions with high RXR expression.
贝沙罗汀（他扎罗汀）是一种视黄酸X受体（RXR）激动剂，可用于治疗T细胞淋巴瘤，其在阿尔茨海默病中的作用机制也备受争议。使用芳基硼酸酯前体1和[(11)C]二氧化碳，通过铜介导的交叉偶联反应，在大气压下合成了碳-11标记的贝沙罗汀（[(11)C-羰基]4-[1-(3,5,5,8,8-五甲基四氢萘-2-基)乙烯基]苯甲酸），基于[(11)C]CO2，未校正的放射化学产率为15±2%（n = 3）。通过明智地选择溶剂、催化剂和添加剂，以及前体浓度和[(11)C]CO2的纯度，成功制备了这种(11)C标记的羧酸。在32分钟内分离出了放射化学纯度>99%的[(11)C]贝沙罗汀（>37 mCi）。初步正电子发射断层扫描-磁共振成像显示，在静脉注射放射性示踪剂后的前75秒内，非人类灵长类动物的大脑快速摄取（注射时比活>0.3 Ci/μmol），随后在60分钟内缓慢清除（Δ=-43%）。在全脑和RXR高表达区域观察到适度摄取（SUVmax = 0.8）。
