Semiautomated radiosynthesis and biological evaluation of [18F]FEAU:: A novel PET imaging agent for HSV1-tk/sr39tk reporter gene expression
Semiautomated radiosynthesis and biological evaluation of [18F]FEAU:: A novel PET imaging agent for HSV1-tk/sr39tk reporter gene expression
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DOI：
10.1007/s11307-007-0122-3
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发表时间：
2008-03-01
影响因子：
3.1
通讯作者：
Gambhir, Sanjiv S.
中科院分区：
文献类型：
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作者：
Chin, Frederick T.;Namavari, Mohammed;Gambhir, Sanjiv S.
2‘-Deoxy-2’-[F-18]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil([F-18]FEAU)是一种应用正电子发射断层扫描技术监测单纯疱疹病毒1型胸苷激酶(HSV1-tk)报告基因表达的放射性标记核苷。然而，具有挑战性的放射合成为能够常规提供[F-18]Feau带来了问题。我们已经开发了一种常规方法，使用商业GE TRACERLab FX-FN放射合成模块和定制的设备来提供[F-18]FEAU。所有放化产额均经衰变校正至轰击结束，并以S+/-SD的平均值报告。经过放射性氟化(33+/-8%；n=4)、溴化(85+/-8%；n=4)、偶联反应(83+/-6%；n=4)、碱解步骤和随后的高效液相层析纯化，得到纯化的[F-18]Feauβ-异构体，总收率为5+/-1%(n=3次)，类似于5.5h，β/α-异构体比率为7.4。放化/化学纯度和比活度分别超过99%和1.3Ci/m o l(48Gbq/m o l)。在细胞培养中，[F-18]FEAU显著高于对照组(P
2'-Deoxy-2'-[F-18]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil ([F-18]FEAU) is a promising radiolabeled nucleoside designed to monitor Herpes Simplex Virus Type 1 thymidine kinase (HSV1-tk) reporter gene expression with positron emission tomography (PET). However, the challenging radiosynthesis creates problems for being able to provide [F-18]FEAU routinely. We have developed a routine method using a commercial GE TRACERlab FX-FN radiosynthesis module with customized equipment to provide [F-18]FEAU. All radiochemical yields are decay corrected to end-of-bombardment and reported as means s +/- SD. Radiofluorination (33 +/- 8%; n=4), bromination (85 +/- 8%; n=4), coupling reaction (83 +/- 6%; n=4), base hydrolysis steps, and subsequent high-performance liquid chromatography purification afforded purified [F-18]FEAU beta-anomer in 5 +/- 1% overall yield (n=3 runs) after similar to 5.5 h and a beta/alpha-anomer ratio of 7.4. Radiochemical/chemical purities and specific activity exceeded 99% and 1.3 Ci/mu mol (48 GBq/mu mol), respectively. In cell culture, [F-18]FEAU showed significantly (P