Kjærgaard Kristoffer, Sandahl Thomas Damgaard, Frisch Kim, Vase Karina Højrup, Keiding Susanne, Vilstrup Hendrik, Ott Peter, Gormsen Lars Christian, Munk Ole Lajord
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark.
EJNMMI Radiopharm Chem. 2020 Jun 18;5(1):15. doi: 10.1186/s41181-020-00100-1.
Copper is essential for enzymatic processes throughout the body. [Cu]copper (Cu) positron emission tomography (PET) has been investigated as a diagnostic tool for certain malignancies, but has not yet been used to study copper homeostasis in humans. In this study, we determined the hepatic removal kinetics, biodistribution and radiation dosimetry of Cu in healthy humans by both intravenous and oral administration.
Six healthy participants underwent PET/CT studies with intravenous or oral administration of Cu. A 90 min dynamic PET/CT scan of the liver was followed by three whole-body PET/CT scans at 1.5, 6, and 20 h after tracer administration. PET data were used for estimation of hepatic kinetics, biodistribution, effective doses, and absorbed doses for critical organs.
After intravenous administration, Cu uptake was highest in the liver, intestinal walls and pancreas; the gender-averaged effective dose was 62 ± 5 μSv/MBq (mean ± SD). After oral administration, Cu was almost exclusively taken up by the liver while leaving a significant amount of radiotracer in the gastrointestinal lumen, resulting in an effective dose of 113 ± 1 μSv/MBq. Excretion of Cu in urine and faeces after intravenous administration was negligible. Hepatic removal kinetics showed that the clearance of Cu from blood was 0.10 ± 0.02 mL blood/min/mL liver tissue, and the rate constant for excretion into bile or blood was 0.003 ± 0.002 min.
Cu biodistribution and radiation dosimetry are influenced by the manner of tracer administration with high uptake by the liver, intestinal walls, and pancreas after intravenous administration, while after oral administration, Cu is rapidly absorbed from the gastrointestinal tract and deposited primarily in the liver. Administration of 50 MBq Cu yielded images of high quality for both administration forms with radiation doses of approximately 3.1 and 5.7 mSv, respectively, allowing for sequential studies in humans.
EudraCT no. 2016-001975-59. Registration date: 19/09/2016.
铜对全身的酶促过程至关重要。铜（Cu）正电子发射断层扫描（PET）已被研究作为某些恶性肿瘤的诊断工具，但尚未用于研究人体中的铜稳态。在本研究中，我们通过静脉内和口服给药确定了健康人体内铜的肝脏清除动力学、生物分布和辐射剂量学。
六名健康参与者接受了静脉内或口服铜的PET/CT研究。在示踪剂给药后，先对肝脏进行90分钟的动态PET/CT扫描，然后在1.5、6和20小时进行三次全身PET/CT扫描。PET数据用于估计肝脏动力学、生物分布、有效剂量和关键器官的吸收剂量。
静脉给药后，肝脏、肠壁和胰腺对铜的摄取最高；性别平均有效剂量为62±5μSv/MBq（平均值±标准差）。口服给药后，铜几乎完全被肝脏摄取，而胃肠道腔内则残留大量放射性示踪剂，导致有效剂量为113±1μSv/MBq。静脉给药后，铜在尿液和粪便中的排泄可忽略不计。肝脏清除动力学表明，铜从血液中的清除率为0.10±0.02 mL血液/分钟/mL肝组织，排泄到胆汁或血液中的速率常数为0.003±0.002分钟。
铜的生物分布和辐射剂量学受示踪剂给药方式的影响，静脉给药后肝脏、肠壁和胰腺摄取较高，而口服给药后，铜迅速从胃肠道吸收并主要沉积在肝脏中。给予50 MBq铜后，两种给药形式均产生了高质量的图像，辐射剂量分别约为3.1和5.7 mSv，从而允许在人体中进行连续研究。
EudraCT编号2016-001975-59。注册日期：2016年9月19日。
