量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum and Radiological Science and Technology.
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【Background / Aims】
Positron emission tomography (PET) imaging is a useful method for analyzing the biological functions of receptors and transporters in the CNS. The Demonstration of functional changes will lead to early diagnosis of various brain diseases. However, it is only accumulation of radioactivity that can be followed by PET, and it is difficult to separate it from off-target binding.
For example, it has been found that some useful agents that bind to the glutamate transporter (GLT) also bind to the estrogen receptor (ER). We excluded off-target binding using computational chemistry techniques and worked on the development of glutamate transporter PET imaging agents.
【Methods】
First, we performed an in silico-binding assay using tamoxifen, which binds to both GLT and ERα proteins using our protein-ligand docking calculations. Next, Structural modifications were then carried out with tetrahydrobenzopyran derivatives predominant in GLT binding, taking note of the binding to ERα. Furthermore, we investigated the position where [18F] or [11C] which is a PET nuclide can be introduced.
【Result】
In silico - binding assay, we designed tamoxifen and derivatives of tetrahydrobenzopyran. I believe that these can be used as ligands for GLT. In our group, design of labeling precursors and examination of labeling conditions are also under way.
【Conclusions】
We performed in silico binding assay and synthesized labeled derivatives of tamoxifen and tetrahydrobenzopyran. This may be a ligand for glutamate transporter. Currently, we are preparing for animal experiments using epilepsy model animals with glutamate metabolism inhibition.
会議概要（会議名, 開催地, 会期, 主催者等）
31st Annual Congress of the European Association of Nuclear Medicine
Development of imaging agent for glutamic acid transporter by off-target exclusion using computational chemical method
