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

PurposeCopper is essential for enzymatic processes throughout the body. [Cu-64]copper (Cu-64) 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-64 in healthy humans by both intravenous and oral administration.MethodsSix healthy participants underwent PET/CT studies with intravenous or oral administration of Cu-64. A 90min dynamic PET/CT scan of the liver was followed by three whole-body PET/CT scans at 1.5, 6, and 20h after tracer administration. PET data were used for estimation of hepatic kinetics, biodistribution, effective doses, and absorbed doses for critical organs.ResultsAfter intravenous administration, Cu-64 uptake was highest in the liver, intestinal walls and pancreas; the gender-averaged effective dose was 625 mu Sv/MBq (meanSD). After oral administration, Cu-64 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 mu Sv/MBq. Excretion of Cu-64 in urine and faeces after intravenous administration was negligible. Hepatic removal kinetics showed that the clearance of Cu-64 from blood was 0.10 +/- 0.02mL blood/min/mL liver tissue, and the rate constant for excretion into bile or blood was 0.003 +/- 0.002min(-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, Cu-64 is rapidly absorbed from the gastrointestinal tract and deposited primarily in the liver. Administration of 50MBq Cu-64 yielded images of high quality for both administration forms with radiation doses of approximately 3.1 and 5.7mSv, respectively, allowing for sequential studies in humans.Trial registration numberEudraCT no. 2016-001975-59. Registration date: 19/09/2016.