Introduction: The radiopharmaceutical 3’-deoxy-3’-[18F]fluorothymidine ([18F]FLT) is a 18F-labeled thymidine analog that serves as an imaging biomarker of cellular proliferation in positron emission tomography. We recently reported a greater-than two-fold increase in radiochemical yield (48±2%, uncorrected) for [18F]FLT utilizing the hindered tertiary alcohol 3-methyl-3-pentanol in the reaction medium and showed the efficacy of this radiotracer in a murine model of pediatric acute myeloid leukemia. In continuing efforts to move this process to human-use in pediatrics, we have developed quality control methods and release criteria for the improved production of [18F]FLT and have validated this new process in preparation for human use. Methods: The radiochemical purity of [18F]FLT was determined via analytical high performance liquid chromatography with radioactivity detection using an Agilent Zorbax Eclipse XDB-C18 column (5mm, 4.6x150mm) in 10% ethanol in water. To ensure the final product was free of residual volatile organic impurities, gas chromatography (GC) was performed using a J & W Carbowax column (30m x 250mm x 0.25mm). In the GC analysis, the final product was compared to a standard solution consisting of 0.1% ethanol, 0.1% acetone, 0.01% acetonitrile, and 0.001% 3-methyl-3-pentanol. The product was also tested for pH to ensure that the final product was within acceptable ranges for injection (6-8). All other tests are consistent with published [18F]FLT release criteria recommendations. Results: The radiochemical purity of the final product was 99.9% (release criteria≥95%). The final product contained 3.6±1.1% ethanol (release criteria&lt;8%) and no traces of acetonitrile or acetone. Additionally, 3-methyl-3-pentanol was not detected in GC analysis (retention time of 2.435min; n=3). The final product was clear, colorless, and pH 6. Conclusion: Based on the QC tests performed in this study, the final formulation of [18F]FLT, synthesized in the improved process which incorporates 3-methyl-3-pentanol, meets the published release criteria recommendations for human use and can now be submitted for regulatory review.

Quality control development for the improved clinical production of 3’-deoxy-3’-[18F]fluorothymidine, which utilizes 3-methyl-3-pentanol, for pediatric cancers

255th National Meeting (2018)

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