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Fluorescence Intensity vs. PET Tracer Uptake in Monitoring Response to Chemotherapeutic Drug in Fluorescent Mouse Mesothelioma Model
https://repo.qst.go.jp/records/69529
https://repo.qst.go.jp/records/69529a118da01-906b-4ade-9aa8-7616702d60aa
Item type | 会議発表用資料 / Presentation(1) | |||||
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公開日 | 2008-10-22 | |||||
タイトル | ||||||
タイトル | Fluorescence Intensity vs. PET Tracer Uptake in Monitoring Response to Chemotherapeutic Drug in Fluorescent Mouse Mesothelioma Model | |||||
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_c94f | |||||
資源タイプ | conference object | |||||
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 |
Saito, Yuriko
× Saito, Yuriko× Furukawa, Takako× Saga, Tsuneo× Arano, Yasushi× Fujibayashi, Yasuhisa× 齋藤 有里子× 古川 高子× 佐賀 恒夫× 荒野 泰× 藤林 康久 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Various anti-cancer drugs are now under development. Well-characterized animal models and in vivo imaging methods would greatly facilitate the evaluation of their effectiveness in the early stage of drug development. Asbestos-induced mesothelioma is a social concern in Japan. Its incidence is expected to peak in 10-20 years. Since there are still few optimal diagnostic and therapeutic protocols, new diagnostic, preventive and therapeutic options for mesothelioma are urgently needed. To facilitate the development of therapeutics, we established fluorescent mesothelioma model in mouse as an in vivo evaluation system for therapeutic effects and characterized the response to the treatment with pemetrexed, an antifolate antineoplastic agent approved for mesothelioma treatment, in fluorescence intensity and uptake of often-used PET tracers, FLT and FDG. We transfected a mesothelioma cell line MSTO-211H with a plasmid encoding red fluorescent protein, DsRed, and established a cell line stably expressing DsRed. The cells formed subcutaneous and pleural tumors in nude mice and the fluorescence intensity detected from outside the body correlated well with the tumor size. When tumor bearing mice were treated with 200 mg/kg pemetrexed for two weeks, tumor growth was significantly inhibited and the fluorescence intensity reflected the change in tumor size. When we examined the uptake of 14C-FDG and 3H-FLT after single dose of pemetrexed, the uptake of 3H-FLT into tumor was significantly increased during 1 to 24 hrs after the treatment. The tumor-to-blood ratio peaked at 12 hrs after the treatment and returned to the initial value in 48 hrs. After consecutive dose of pemetrexed for two weeks, the uptake of 3H-FLT into tumor was about four times higher than untreated one at 24 hrs after the last pemetrexed treatment. The increased uptake of FLT is likely caused by the inhibition of de novo synthesis of DNA by pemetrexed and the compensative upregulation of salvage pathway. In contrast, the uptake pattern of 14C-FDG into treated tumor showed no significant differences to the control tumor after single or consecutive dose of pemetrexed. In fluorescent tumor model, fluorescence intensity can be used to monitor tumor size, whereas tumor uptake of FLT could be a suitable marker of the response to pemetrexed, and probably other anti-folate chemotherapeutics. Our results also suggest the possibility that FLT can be used to monitor the early tumor response to pemetrexed in patients to optimize the dose and/or treatment protocol. |
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会議概要(会議名, 開催地, 会期, 主催者等) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Annual Congress of the European Association of Nuclear Medicine 2008 | |||||
発表年月日 | ||||||
日付 | 2008-10-15 | |||||
日付タイプ | Issued |