- 期刊
癌症正子造影劑F-18 FCH之發展與製程改善：台大醫院正子中心之經驗分享
Development and Improvement of Oncologic Tracer F-18 FCH for Positron Emission Tomography: Experience of PET Center of National Taiwan University Hospital
摘要
除了臨床使用廣泛的正子造影劑F-18 FDG，氟-18標誌之膽鹼衍生物F-18 fluoromethylcholine (F-18 FCH)也已應用於癌症診斷，尤其是某些易造成F-18 FDG偽陽性攝取之腫瘤，如肝癌或攝護腺癌。因應臨床需求，台大醫院正子中心已於2008年已初步生產F-18 FCH。但是，針對2012年台大醫院開始之F-18 FCH多中心phase III應用於肝癌之臨床試驗，現有F-18 FCH之放化產量卻明顯不足以同時提供其他北部參與此試驗之醫院，並進而將造成F-18 FCH生產成本大幅提高之問題。另外，目前國內外藥典皆無記載F-18 FCH之品管方法。因此，本中心嘗試改進F-18 FCH之自動化生產以期使放化產率提高，並且進一步建立其品管方法以確定其臨床使用上之安全性與有效性。其中，我們改良先前文獻報導的合成方法之外，更改裝現有的TRACERLab FXFN硬體設備以進行F-18 FCH之兩步合成反應，並將此自動合成系統達到一最佳化。而臨床品管方面，我們則進行一系列F-18 FCH的物化及生物測試，例如放射化學純度，殘餘溶劑測試及無熱原測試等。目前，F-18 FCH放化產率在合成結束時平均為18.8 ± 2.1% (n = 27, EOB)且反應時間為49 ± 5分鐘。甚者，其化學不純物DMAE 的平均殘餘量可降低為10 ppm以下。目前，本中心可以一次生產出更多且安全有效的F-18 FCH以供癌症研究或臨床診斷使用。甚者，此自動合成裝置也已獲得台灣專利核可，希望能讓台灣更多的研究單位與醫療機構、更多的癌症病患與家庭受益。
並列摘要
The glucose analog, F-18 fluorodeoxyglucose (F-18 FDG) is the most widely used radiopharmaceutical for tumor imaging. However, its diagnostic accuracy and specificity for certain cancers, such as prostate cancer and hepatocellular carcinoma (HCC) are relatively low. Because of the clinical need, we have automatically produced F-18 Fluoromethylcholine (F-18 FCH) for our preliminary clinical studies since 2008. However, for the upcoming phase III, a multi-center study of F-18 FCH for HCC in 2012, the current radiochemical yield (RCY) of F-18 FCH was too low to supply other near-by hospitals involved in this clinic trial. Moreover, Chinese Pharmacopoeia or U.S. Pharmacopoeia does not define the procedure for quality control (QC) of F-18 FCH for human use. As a result, we improved the production method of F-18 FCH to achieve higher RCY. Not only we modified TRACERlab FXFN module based on two-step procedure of F-18 FCH, but also all the reaction parameters were systematically studied. In addition, we also set a series of QC tests to assure the safety and efficacy of F-18 FCH. After improvement and optimization of F-18 FCH production, the RCY of F-18 FCH was 18.8 ± 2.1% (n = 27, EOB) in a synthesis time of 49 ± 5 min, and the residual DMAE concentrations of each F-18 FCH production was less than 10 ppm. Now, this improved method could be dedicated for the demand in clinic use of F-18 FCH, especially for nearby study sites without a cyclotron. Moreover, Taiwan patent for the improved F-18 FCH synthesis method has been approved and hope it could be helpful to other medical institutes for the benefits of other patients and families.