Zhang Yiding, Kumata Katsushi, Xie Lin, Kurihara Yusuke, Ogawa Masanao, Kokufuta Tomomi, Nengaki Nobuki, Zhang Ming-Rong
Department of Advanced Nuclear Medicine Sciences, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
SHI Accelerator Service, Ltd., 7-1-1 Nishigotanda, Shinagawa-ku, Tokyo 141-0031, Japan.
Pharmaceuticals (Basel). 2023 Jul 5;16(7):963. doi: 10.3390/ph16070963.
Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) is a selective inhibitor of glutaminase-1 (GLS1), consequently inhibiting glutaminolysis. BPTES is known for its potent antitumor activity and plays a significant role in senescent cell removal. In this study, we synthesized [C-carbonyl]BPTES ([C]BPTES) as a positron emission tomography (PET) probe for the first time and assessed its biodistribution in mice using PET. [C]BPTES was synthesized by the reaction of an amine precursor () with [C-carbonyl]phenylacetyl acid anhydride ([C]), which was prepared from [C]CO and benzyl magnesium chloride, followed by in situ treatment with isobutyl chloroformate. The decay-corrected isolated radiochemical yield of [C]BPTES was 9.5% (based on [C]CO) during a synthesis time of 40 min. A PET study with [C]BPTES showed high uptake levels of radioactivity in the liver, kidney, and small intestine of mice.
双-2-(5-苯乙酰氨基-1,3,4-噻二唑-2-基)乙基硫醚（BPTES）是谷氨酰胺酶-1（GLS1）的选择性抑制剂，因此可抑制谷氨酰胺分解代谢。BPTES以其强大的抗肿瘤活性而闻名，并且在清除衰老细胞中发挥重要作用。在本研究中，我们首次合成了[C-羰基]BPTES（[C]BPTES）作为正电子发射断层扫描（PET）探针，并使用PET评估了其在小鼠体内的生物分布。[C]BPTES通过胺前体（）与[C-羰基]苯乙酰酸酐（[C]）反应合成，[C-羰基]苯乙酰酸酐由[C]CO和苄基氯化镁制备，然后用氯甲酸异丁酯进行原位处理。在40分钟的合成时间内，[C]BPTES经衰变校正后的分离放射化学产率为9.5%（基于[C]CO）。用[C]BPTES进行的PET研究显示，小鼠肝脏、肾脏和小肠中放射性摄取水平较高。
