Intravenous and oral copper kinetics, biodistribution and dosimetry in healthy humans studied by [(64)Cu]copper PET/CT

PURPOSE: Copper is essential for enzymatic processes throughout the body. [(64)Cu]copper ((64)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 (64)Cu in healthy humans by both intravenous and oral administration. METHODS: Six healthy participants underwent PET/CT studies with intravenous or oral administration of (64)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. RESULTS: After intravenous administration, (64)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, (64)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 (64)Cu in urine and faeces after intravenous administration was negligible. Hepatic removal kinetics showed that the clearance of (64)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(− 1). CONCLUSION: (64)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, (64)Cu is rapidly absorbed from the gastrointestinal tract and deposited primarily in the liver. Administration of 50 MBq (64)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. TRIAL REGISTRATION NUMBER: EudraCT no. 2016–001975-59. Registration date: 19/09/2016.