Suzuki Masaaki, Takashima-Hirano Misato, Ishii Hideki, Watanabe Chika, Sumi Kengo, Koyama Hiroko, Doi Hisashi
Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology Center, 35, Gengo Morioka-cho, Obu-shi, Aichi 474-8511, Japan; RIKEN Center for Molecular Imaging Science (CMIS), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
RIKEN Center for Molecular Imaging Science (CMIS), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Bioorg Med Chem Lett. 2014 Aug 1;24(15):3622-5. doi: 10.1016/j.bmcl.2014.05.041. Epub 2014 Jun 2.
Retinoids are a class of chemical compounds which include both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Both experimental and clinical studies have revealed that retinoids regulate a wide variety of essential biological processes. In this study, we synthesized (11)C-labeled all-trans-retinoic acid (ATRA), the most potent biologically active metabolite of retinol and used in the treatment of acute promyelocytic leukemia. The synthesis of (11)C-labeled ATRA was accomplished by a combination of rapid Pd(0)-mediated C-[(11)C]methylation of the corresponding pinacol borate precursor prepared by 8 steps and hydrolysis. [(11)C]ATRA will prove useful as a PET imaging agent, particularly for elucidating the improved therapeutic activity of ATRA (natural retinoid) for acute promyelocytic leukemia by comparing with the corresponding PET probe [(11)C]Tamibarotene (artificial retinoid).
维甲酸是一类化合物，包括天然膳食维生素A（视黄醇）代谢物和活性合成类似物。实验研究和临床研究均表明，维甲酸可调节多种重要的生物学过程。在本研究中，我们合成了碳-11标记的全反式维甲酸（ATRA），它是视黄醇最具生物活性的代谢物，用于治疗急性早幼粒细胞白血病。碳-11标记的ATRA通过以下方法合成：首先通过8步反应制备相应的频哪醇硼酸酯前体，然后进行快速钯（0）介导的碳-11甲基化反应，最后水解。碳-11标记的ATRA将被证明是一种有用的正电子发射断层扫描（PET）成像剂，特别是通过与相应的PET探针碳-11标记的他米巴罗汀（人工合成维甲酸）比较，来阐明ATRA（天然维甲酸）对急性早幼粒细胞白血病的治疗活性改善情况。
