| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-06-16 |
| タイトル |
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タイトル |
Development of a Novel Positron Emission Tomography Probe Deuterated [18F]FE-TMP ([18F]FE-TMP-d4), an Antagonist of Escherichia coli Dihydrofolate Reductase, for Reporter Gene Imaging of the Brain |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Fujinaga Masayuki
Takayuki Ohkubo
Shimojo Masafumi
Nagai Yuji
Ono Maiko
Matsushita Yumi
Mimura Koki
Mori Wakana
Yiding Zhang
Yusuke Kurihara
Ogawa Masanao
Nengaki Nobuki
Minamimoto Takafumi
Higuchi Makoto
Yamasaki Tomoteru
Zhang Ming-Rong
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
[18F]Fluoroethoxy trimethoprim ([18F]FE-TMP, [18F]2), a unique antagonist of bacterial dihydrofolate reductase (ecDHFR), has been developed as a reporter gene imaging agent. Here, we developed new PET probes based on TMP. Simulations predicted that hydrophobic interactions around the benzene ring of 2 contributed to binding with ecDHFR. The more lipophilic fluoropropyl-TMP analog (3) showed a higher binding affinity for ecDHFR than 2. However, 18F-labeled 3 ([18F]3) underwent 18F-defluorination during PET imaging of ecDHFR-transfected mice. Subsequently, we evaluated FE-d4 analog (5) as a candidate exhibiting greater in vivo stability than 2. Metabolite analysis showed a lower contamination of radiolabeled metabolites in mouse brains with 18F-labeled 5 ([18F]5) than [18F]2. PET imaging with [18F]5 of a non-human primate brain was characterized by a distinct signal/noise ratio, which allowed in vivo visualization of brain circuits expressing the reporter gene, demonstrating the superior potential of [18F]5 as a PET probe for reporter gene imaging of the brain. |
| 書誌情報 |
Journal of Medicinal Chemistry
発行日 2025-06
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| 出版者 |
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出版者 |
American Chemical Society |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0022-2623 |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.1021/acs.jmedchem.5c00613 |
