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

Authors
  • Tateishi, Hiroyuki1
  • Tsuji, Atsushi B2
  • Kato, Koichi3
  • Sudo, Hitomi4
  • Sugyo, Aya4
  • Hanakawa, Takashi5
  • Zhang, Ming-Rong6
  • Saga, Tsuneo7
  • Arano, Yasushi8
  • Higashi, Tatsuya4
  • 1 Experimental Nuclear Medicine Team, Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan; Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. , (Japan)
  • 2 Experimental Nuclear Medicine Team, Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. Electronic address: [email protected] , (Japan)
  • 3 Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan; Department of Integrative Brain Imaging, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-5551, Japan. Electronic address: [email protected] , (Japan)
  • 4 Experimental Nuclear Medicine Team, Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. , (Japan)
  • 5 Department of Integrative Brain Imaging, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-5551, Japan. , (Japan)
  • 6 Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. , (Japan)
  • 7 Experimental Nuclear Medicine Team, Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan; Department of Diagnostic Radiology, Kyoto University Hospital, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. , (Japan)
  • 8 Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. , (Japan)
Type
Published Article
Journal
Bioorganic & medicinal chemistry letters
Publication Date
Nov 01, 2017
Volume
27
Issue
21
Pages
4893–4897
Identifiers
DOI: 10.1016/j.bmcl.2017.09.033
PMID: 28951078
Source
Medline
Keywords
License
Unknown

Abstract

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 [11C]2 showed low tumor accumulation, probably due to adduct formation with plasma proteins, [11C]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.

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