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題名 | 探討氟-18胸腺嘧啶核苷合成方法之改進=A Study of Modified Approach of Synthesizing 3'-Deoxy-3'-F-18 Fluorothymidine |
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作者 | 許耘萱; 黃羿嘉; 蘇博仁; 廖曉薇; 林秀鈴; 張圍茗; 陳泰賓; 丁慧枝; 陳輝墉; | 書刊名 | Annals of Nuclear Medicine and Molecular Imaging |
卷期 | 27:1 2014.03[民103.03] |
頁次 | 頁28-36 |
分類號 | 414.93 |
關鍵詞 | 氟-18胸腺嘧啶核苷; 前驅物; 惡性腫瘤細胞增殖; F-18 FLT; 3'-deoxy-3' fluorothymidine; Precursor; Tumor cell proliferation; |
語文 | 中文(Chinese) |
中文摘要 | 背景:使用氟-18胸腺嘧啶核苷(3'-deoxy-3'fluorothymidine, F-18FLT)進行正子電腦斷層掃描(PET/CT)已被證實可以用非侵襲性造影之方法評估惡性腫瘤細胞增殖(cellproliferation),其可彌補臨床上廣泛使用評估惡性腫瘤之氟-18去氧葡萄糖(F-18 FDG)正子電腦斷層掃描特異性之不足。F-18 FLT之攝取已被證實與通常用以評估惡性腫瘤細胞增殖之指標-Ki67 score有密切正相關。然而現在有之F-18 FLT之合成方法既耗時且合成率低,不利於臨床應用之推廣。因此本研究針對F-18 FLT之合成加以修訂其合成條件,期能減少合成時間及提高產率。方法:本研究以市售之前驅物{3-N-t-Butoxycarbonyl-[5'-O-(4,4'-dimethoxytrityl-2'-deoxy-3'-O-nosyl-β-D-threopentofuranosyl)] thymine},以親核性方法(Nucleophilic substitution)用與50~300 mCi的F-18標記,在不同之前驅物濃度(20mg、30mg)不同之反應時間(5分鐘、10分鐘),反應溫度為120之條件下進行F-18 FLT之合成,並以薄層分析法(TLC)探討合成率、HPLC探究其化學純度。結果:本研究使用前述之前驅物在濃度為30 mg,反應時間為10分鐘之條件下產率最高,平均為31.27±8.07%。結論:本研究中使用的F-18放射活度並不會影響產率(未作放射活度校正),製備時間全程小於1小時。另外,考量F-18 FLT合成之產率及經濟效益,選擇20 mg Precursor於120°C反應10分鐘之條件進行合成,隨後以HPLC進行分離純化,其平均化學純度為64.79%(n=4)。 |
英文摘要 | Background: F-18 FLT(3'-deoxy-3'fluorothymidine) turned out to be a tracer particularly suitable for PET/CT imaging of tumor cell proliferation because of the longer half-life of fluorine-18 and lacking metabolic degradation in vivo. In recent imaging studies, the biochemical rationale of F-18 FLT for clinical application in PET/CT assessment of tumor proliferation were demonstrated. Until now, the clinical applicability of F-18 FLT has been limited by the lengthy synthesis of the precursor, the low reproducibility and low radiochemical yield rate.Methods: We investigated a commercially available precursor, {3-N-t-Butoxycarbonyl-[5'-O(4, 4'-dimethoxytrityl-2'-deoxy-3'-O-nosyl-β-D-threo pentofuranosyl)]thymine}, using a common approach for introducing the label with nucleophilic F-18 fluoride. Radiochemical yields were determined in dependence on substrate concentration, reaction time at reaction temperature of 120°C. The product solutions were analyzed by thin layer chromatography using silica gel plates. The other hand radiochemical purity was analyzed by high performance liquid chromatography (HPLC) using silica gel plates.Results: The best F-18 FLT mean yields were 31.3±8.7% at 30 mg precursor with 10 minutes reaction time, independent of F-18 fluoride radioactivity. We achieved satisfactory radiochemical yields of 31.27±8.07%, radiochemical purification of 64.79% (n=4) within 60 minutes of preparation time.Conclusion: This study allow F-18 FLT synthesis without lengthy preparation of the precursor and with high reproducibility mandatory for clinical application. |
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