Synthesis and evaluation of 11C-labeled coumarin analog as an imaging probe for detecting monocarboxylate transporters expression

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:27

Article

Tateishi, Hiroyuki^1,5  Tsuji, Atsushi B.¹  Kato, Koichi^2,3  Sudo, Hitomi¹  Sugyo, Aya¹  Hanakawa, Takashi³  Zhang, Ming-Rong²  Saga, Tsuneo^1,4  Arano, Yasushi⁵  Higashi, Tatsuya¹ 

[1] Natl Inst Quantum & Radiol Sci & Technol QST NIRS, Natl Inst Radiol Sci, Expt Nucl Med Team,Dept Mol Imaging & Theranost, Inage Ku, 4-9-1 Anagawa, Chiba 2638555, Japan

[2] Natl Inst Quantum & Radiol Sci & Technol QST NIRS, Natl Inst Radiol Sci, Dept Radiopharmaceut Dev, Inage Ku, 4-9-1 Anagawa, Chiba 2638555, Japan

[3] Natl Ctr Neurol & Psychiat, Dept Integrat Brain Imaging, 4-1-1 Ogawahigashi Cho, Kodaira, Tokyo 1875551, Japan

[4] Kyoto Univ Hosp, Dept Diagnost Radiol, Sakyo Ku, 54 Shogoinkawahara Cho, Kyoto 6068507, Japan

[5] Chiba Univ, Grad Sch Pharmaceut Sci, Dept Mol Imaging & Radiotherapy, Chuo Ku, 1-8-1 Inohana, Chiba 2608675, Japan

关键词: Positron emission tomography;    Fluorescence;    Cancer;    Astrocyte-neuron lactate shuttle;    Radiosynthesis;   

DOI  :  10.1016/j.bmcl.2017.09.033

来源: Elsevier

【 摘 要 】

Upregulated monocarboxylate transporters (MCTs) in tumors are considered diagnostic imaging targets. Herein, we synthesized the positron emission tomography probe candidates coumarin analogs 2 and 3, and showed 55 times higher affinity of 2 for MCTs than a representative MCT inhibitor. Whereas [C-11] 2 showed low tumor accumulation, probably due to adduct formation with plasma proteins, [C-11] 2 showed high initial brain uptake, suggesting that the scaffold of 2 has properties that are preferable in imaging probes for the astrocyte-neuron lactate shuttle. Although further optimization of 2 is required, our findings can be used to inform the development of MCT-targeted imaging agents. (C) 2017 The Author(s). Published by Elsevier Ltd.

【 授权许可】

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