Automated Synthesis, Quality Control, and Preliminary Application of ¹⁸F-DPA-714 in a Traumatic Brain Injury Model

Objective: To establish an automated synthesis process for ¹⁸F-DPA-714, validate its quality, and conduct preliminary imaging verification of inflammation in a traumatic brain injury model. Methods: Using a Sumitomo CFN fluorine multifunctional synthesis module from Japan, ¹⁸F-DPA-714 was synthesized via nucleophilic substitution with pre-DPA-714 as the precursor. After optimizing reaction conditions, the product was purified by semi-preparative High-Performance Liquid Chromatography (HPLC) with a mobile phase of 45% acetonitrile/0.1% trifluoroacetic acid (TFA), concentrated on a C18 solid-phase extraction (SPE) cartridge, and finally sterile-filtered to obtain the injectable solution. Three batches of the product underwent quality control (QC) assessments, including radiochemical yield (RCY), radiochemical purity (RCP), pH, residual solvents (acetonitrile, K_2.2.2), sterility, and bacterial endotoxin levels. Results: The results indicated that the optimal synthesis conditions for ¹⁸F-DPA-714 were as follows: the reaction temperature is 100 ℃, the reaction time is 10 min, and the precursor amount is 2 mg. The total synthesis time, from the drying of ¹⁸F-fluoride to the final product, was approximately 45 min, exhibiting an uncorrected radiochemical yield of (42.5±3.2)% (n=30) and a radiochemical purity ＞99%. The final formulation was a clear, colorless solution (pH 5.57.0) with residual acetonitrile ＜0.04% and K_2.2.2 ＜50 μg/mL, ethanol content ＜10%, specific activity 80-102 GBq/μmol, and it complied with the Chinese Pharmacopoeia standards for sterility and bacterial endotoxins. Preliminary inflammatory imaging validation in traumatic brain injury models in this study further confirmed the potential of ¹⁸F-DPA-714 for neuroinflammation assessment. The preparation process adopted in this work was completed using an existing automated synthesis module (Sumitomo CFN), demonstrating good reproducibility (n≥30) and stable, reliable product quality, which can meet the quality requirements for future clinical applications.