posted Sep 16, 2008, 11:14 PM by 林昆儒
updated Sep 17, 2008, 3:59 AM
這次在法國尼斯開會也見到了實驗室的老面孔 葉信顯(第一屆畢業生), 信顯目前在 Gelovani, Juri G
位於Department of Experimental Diagnostic Imaging, University of Texas MD Anderson Cancer Center 的實驗室工作, 正在攻讀博士, 這一次在大會也有兩篇 oral presentation 相當優秀!
|N(3)-Substituted thymidine analogues V: Synthesis and preliminary PET imaging of N(3)-[(18)F]fluoroethyl thymidine and N(3)-[(18)F]fluoropropyl thymidine.|
|Gelovani, Juri G; Soghomonyan, Suren; Alauddin, Mian M; Volgin, Andrei Y; Mukhopadhyay, Uday; Yeh, Hsin Hsien; Flores, Leo G; Shavrin, Aleksandr; |
|Department of Experimental Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.|
|INTRODUCTION: [(18)F]-Labeled analogues of thymidine have demonstrated efficacy for PET imaging of cellular proliferation. We have synthesized two [(18)F]-labeled N(3)-substituted thymidine analogues, N(3)-[(18)F]fluoroethyl thymidine (N(3)-[(18)F]-FET) and N(3)-[(18)F]fluoropropyl thymidine (N(3)-[(18)F]-FPrT), and performed preliminary PET imaging studies in tumor-bearing mice. METHODS: Thymidine was converted to its 3',5'-O-bis-tetrahydropyranyl ether, which was then converted to the N(3)-ethyl and propyl-substituted mesylate precursors. Reactions of these mesylate precursors with n-Bu(4)N[(18)F] or K[(18)F]/kryptofix followed by acid hydrolysis and HPLC purification yielded N(3)-[(18)F]-FET and N(3)-[(18)F]-FPrT, respectively. Subcutaneous (sc) xenografts of H441 human non-small cell lung cancer were established in two groups of mice (each n=6). Micro-PET images of the tumor-bearing animals were acquired after intravenous injection of N(3)-[(18)F]-FET or N(3)-[(18)F]-FPrT (3700 KBq/animal). RESULTS: The radiochemical yields were 2-12% (d.c.) for N(3)-[(18)F]-FET and 30-38% (d.c.) for N(3)-[(18)F]-FPrT. Radiochemical purity was >99% and calculated specific activity was >74 GBq/mumol at the end of synthesis. The accumulation of N(3)-[(18)F]-FET and N(3)-[(18)F]-FPrT in the tumor tissue at 2 h postinjection was 1.81+/-0.78 and 2.95+/-1.14 percent injected dose per gram (%ID/g), respectively; tumor/muscle ratios were 5.57+/-0.82 and 7.69+/-2.18, respectively; the unidirectional influx rates (K(i)) were 0.013 and 0.018 ml/g per minute, respectively. CONCLUSION: Two novel [(18)F]- N(3)-substituted thymidine analogues have been synthesized in good yields, high purity and high specific activity. Preliminary in vivo studies demonstrated the efficacy of these [(18)F]- N(3)-substituted thymidine analogues for PET imaging of tumors.|