Automatic Synthesis and Preliminary Imaging Study of ¹¹C-Donepezil

A radiotracer, ¹¹C-donepezil (¹¹C-DNP) was synthesized by a fully automatic method, and its biodistribution characteristics were assessed in normal Kunming mice. Dynamic Micro PET/CT imaging was performed in normal Sprague-Dawley (SD) rats to generate time-activity curves, and the PET/CT study was conducted in heart failure model pigs. The radiotracer ¹¹C-DNP was synthesized using the Triflate-¹¹CH₃ method. The crude product was purified by semi-preparative high-performance liquid chromatography (HPLC). Radiochemical purity and specific activity of the final product were assessed using radio-HPLC analysis. Pharmacokinetic characteristics were determined using a combination of biodistribution studies and dynamic micro-PET/CT imaging experiments. The feasibility of using ¹¹C-DNP for cardiac parasympathetic nerve imaging was validated in heart failure model pigs using PET/CT. An automated synthesis process was established using a carbon multifunctional synthesis module, achieving a total synthesis time of approximately 40 minutes, a radiochemical yield of (13.90±2.50)%, radiochemical purity > 99%, and a specific activity of (48.88±4.20) GBq/mmol. Biodistribution experiments conducted in normal Kunming mice demonstrated rapid uptake in the heart and lungs, with the highest heart-to-lung ratio (approximately 1.61:1) observed at 10 minutes post-injection. Dynamic Micro PET/CT imaging in normal Sprague-Dawley (SD) rats revealed significant radiotracer accumulation in tissues rich in acetylcholinesterase nerve fibers. Time-activity curves of major organs indicated that the tracer was primarily metabolized via the hepatobiliary and urinary systems. PET/CT imaging in heart failure model pigs identified multiple regions of sparse or deficient radiotracer uptake within the left ventricle.The automated synthesis of ¹¹C-DNP was successfully achieved, characterized by high radiochemical yield and specific activity. Pharmacokinetic analysis confirmed its rapid metabolism in tissues enriched with acetylcholinesterase nerve fibers. PET/CT imaging in heart failure model pigs accurately reflected the extent of cardiac nerve damage.