11C-多奈哌齐的自动化合成与显像初步研究

Automatic Synthesis and Preliminary Imaging Study of 11C-Donepezil

  • 摘要: 为实现11C-多奈哌齐(11C-DNP)的全自动化合成,并测定其在正常昆明小鼠体内生物分布,正常SD大鼠动态Micro PET/CT显像和时间-活度曲线绘制,心衰模型猪的PET/CT心肌显像研究。本研究采用Triflate-11CH3法制备11C-DNP,粗产品经半制备高效液相色谱纯化得到终产物,经Radio-HPLC测定其放化纯度和比活度;生物分布实验和动态Micro PET/CT显像实验共同确定其药代动力学过程,心衰模型猪的PET/CT显像确定其用于心脏副交感神经成像的可行性。结果表明,通过碳多功能合成模块实现了11C-DNP的自动化合成,总合成时间约40 min,放射化学产率(13.90±2.50)%,放化纯度>99%,比活度(48.88±4.20) GBq/mmol;正常昆明小鼠体内生物分布实验结果显示,心脏和肺能快速达到峰值,在注射显像剂后10 min时心肺比最高(约1.61/1);正常SD大鼠动态Micro PET/CT显像结果显示,在富含乙酰胆碱酯酶神经纤维的组织内放射性摄取均较高,从主要器官的时间-活度曲线得知该显像剂经肝胆和尿路系统代谢;心衰模型猪的PET/CT显像可见左心室多处显像剂摄取稀疏-缺损。以上结果表明,在国产碳多功能合成器上全自动化制备了11C-DNP,其放射化学产率、比活度较高,药代动力学研究结果示其在富含乙酰胆碱酯酶神经纤维的组织内有较高的代谢,心衰模型猪的PET/CT显像可较好的反映心脏副交感神经的受损情况。

     

    Abstract: 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.

     

/

返回文章
返回