Development and Improvement of Oncologic Tracer F-18 FCH for Positron Emission Tomography: Experience of PET Center of National Taiwan University Hospital

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.