Tracing of the Bile-Chemotactic Migration of Juvenile Clonorchis sinensis in Rabbits by PET-CT

BackgroundAdult Clonorchis sinensis live in the bile duct and cause clonorchiasis. It is known that the C. sinensis metacercariae excyst in the duodenum and migrate up to the bile duct through the common bile duct. However, no direct evidence is available on the in vivo migration of newly excysted C. sinensis juveniles (CsNEJs). Advanced imaging technologies now allow the in vivo migration and localization to be visualized. In the present study, we sought to determine how sensitively CsNEJs respond to bile and how fast they migrate to the intrahepatic bile duct using PET-CT. Methodology/Principal FindingsCsNEJs were radiolabeled with 18F-fluorodeoxyglucose (18F-FDG). Rabbits with a gallbladder contraction response to cholecystokinin-8 (CCK-8) injection were pre-screened using cholescintigraphy. In these rabbits, gallbladders contracted by 50% in volume at an average of 11.5 min post-injection. The four rabbits examined were kept anesthetized and a catheter inserted into the mid duodenum. Gallbladder contraction was stimulated by injecting CCK-8 (20 ng/kg every minute) over the experiment. Anatomical images were acquired by CT initially and dynamic PET was then carried out for 90 min with a 3-min acquisition per frame. Twelve minutes after CCK-8 injection, about 3,000 18F-FDG-labeled CsNEJs were inoculated into the mid duodenum through the catheter. Photon signals were detected in the liver 7–9 min after CsNEJs inoculation, and these then increased in the whole liver with stronger intensity in the central area, presenting that the CsNEJs were arriving at the intrahepatic bile ducts. ConclusionIn the duodenum, CsNEJs immediately sense bile and migrate quickly with bile-chemotaxis to reach the intrahepatic bile ducts by way of the ampulla of Vater.研究背景：华支睾吸虫（Clonorchis sinensis）成虫寄生于胆管，可引发华支睾吸虫病（clonorchiasis）。已知华支睾吸虫囊蚴在十二指肠内脱囊，并经胆总管向上迁移至胆管，但目前尚无关于新生脱囊华支睾吸虫幼虫（newly excysted C. sinensis juveniles, CsNEJs）体内迁移过程的直接证据。如今先进的成像技术可实现体内迁移与定位的可视化。本研究旨在通过正电子发射计算机断层显像-计算机断层扫描（PET-CT），探究CsNEJs对胆汁的响应敏感性，以及其向肝内胆管迁移的速度。 材料与方法及主要研究结果：研究人员使用18F-氟代脱氧葡萄糖（18F-fluorodeoxyglucose, 18F-FDG）对CsNEJs进行放射性标记。首先通过胆囊闪烁显像（cholescintigraphy）预先筛选出对八肽胆囊收缩素（cholecystokinin-8, CCK-8）注射具有胆囊收缩反应的家兔：注射后平均11.5分钟时，受试家兔的胆囊体积收缩50%。对4只家兔实施持续麻醉，并于十二指肠中段置入导管。实验全程通过每分钟注射20 ng/kg的CCK-8刺激胆囊收缩。首先通过CT获取解剖影像，随后开展时长90分钟的动态PET扫描，每帧采集时长为3分钟。在CCK-8注射后12分钟，通过导管向十二指肠中段接种约3000个经18F-FDG标记的CsNEJs。CsNEJs接种后7~9分钟，即可在肝脏内检测到光子信号；随后全肝的信号强度逐渐升高，且中央区域信号更强，表明CsNEJs已抵达肝内胆管。 研究结论：在十二指肠内，CsNEJs可迅速感知胆汁，并通过胆汁趋化作用快速迁移，经Vater壶腹（ampulla of Vater）到达肝内胆管。