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Preparation and Evaluation of Ethyl [18F]Fluoroacetate as a Proradiotracer of [18F]Fluoroacetate for the Measurement of Glial Metabolism by PET
https://repo.qst.go.jp/records/45535
https://repo.qst.go.jp/records/45535c4957195-5d6f-4c9b-8352-61aadfefd561
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2009-06-15 | |||||
| タイトル | ||||||
| タイトル | Preparation and Evaluation of Ethyl [18F]Fluoroacetate as a Proradiotracer of [18F]Fluoroacetate for the Measurement of Glial Metabolism by PET | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Mori, Tetsuya
× Mori, Tetsuya× Kobayashi, Masato× Kiyono, Yashushi× Okazawa, Hidehiko× Furukawa, Takako× Fujibayashi, Yasuhisa× et.al× 古川 高子 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Introduction: Changes in glial metabolism in brain ischemia, Alzheimer's disease, depression, schizophrenia, epilepsy and manganese neurotoxicity have been reported in recent studies. Therefore, it is very important to measure glial metabolism in vivo for the elucidation and diagnosis of these diseases. Radiolabeled acetate is a good candidate for this purpose, but acetate has little uptake in the brain due to its low lipophilicity. We have designed a new proradiotracer, ethyl [18F]fluoroacetate ([18F]EFA), which is [18F]fluoroacetate ([18F]FA) esterified with ethanol, to increase the lipophilicity of fluoroacetate (FA), allowing the measurement of glial metabolism. Methods: The synthesis of [18F]EFAwas achieved using ethyl O-mesyl-glycolate as precursor. The blood–brain barrier permeability of ethyl [1-14C]fluoroacetate ([14C]EFA) was estimated by a brain uptake index (BUI) method. Hydrolysis of [14C]EFA in the brain was calculated by the fraction of radioactivity in lipophilic and water fractions of homogenized brain. Using the plasma of five animal species, the stability of [14C]EFA was measured. Biodistribution studies of [18F]EFA in ddY mice were carried out and compared with [18F]FA. Positron emission tomography (PET) scanning using common marmosets was performed for 90 min postadministration. At 60 min postinjection of [18F]EFA, metabolite studies were performed. Organs were dissected from the marmosets, and extracted metabolites were analyzed with a thin-layer chromatography method. Results: The synthesis of [18F]EFA was accomplished in a short time (29 min) and with a reproducible radiochemical yield of 28.6+/-3.6% (decay corrected) and a high radiochemical purity of more than 95%. In the brain permeability study, the BUI of [14C]EFA was 3.8 times higher than that of sodium [1-14C]fluoroacetate. [14C]EFA was hydrolyzed rapidly in rat brains. In stability studies using the plasma of five animal species, [14C]EFA was stable only in primate plasma. Biodistribution studies in mice showed that the uptake of [18F]EFA in selected organs was higher than that of [18F]FA. From nonprimate PET studies, [18F]EFAwas initially taken into the brain after injection. Metabolites related to the tricarboxylic acid (TCA) cycle were detected in common marmoset brain. Conclusion: [18F]EFA rapidly enters the brain and is then converted into TCA cycle metabolites in the brains of common marmosets. [18F] EFA shows promise as a proradiotracer for the measurement of glial metabolism. |
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| 書誌情報 |
Nuclear Medicine and Biology 巻 36, 号 2, p. 155-162, 発行日 2009-02 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0969-8051 | |||||
