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Intravenous and oral copper kinetics, biodistribution and dosimetry in healthy humans studied by [64Cu]copper PET/CT
Kristoffer Kjærgaard
Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital; Department of Hepatology and Gastroenterology, Aarhus University Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6440-2784
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at EJNMMI Radiopharmacy and Chemistry.
Purpose: Copper is essential for enzymatic processes throughout the body. [64Cu]copper (64Cu) 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 64Cu in healthy humans by both intravenous and oral administration.
Methods: Six healthy participants underwent PET/CT studies with intravenous or oral administration of 64Cu. 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, 64Cu 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, 64Cu 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 64Cu in urine and faeces after intravenous administration was negligible. Hepatic removal kinetics showed that the clearance of 64Cu 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: 64Cu 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, and after oral administration, 64Cu is rapidly absorbed from the gastrointestinal tract and deposited primarily in the liver. Administration of 50 MBq 64Cu yielded images of high quality for both administration forms with radiation doses 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.
Keywords
64Cu, copper, kinetics, dosimetry, biodistribution
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CURRENT STATUS: Published
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Posted 01 Jun, 2020
Published
On 18 Jun, 2020
No community comments so far
Editorial decision: Accept
On 25 May, 2020
Editor assigned
On 24 May, 2020
Submission checks complete
On 23 May, 2020
Editor invited
On 23 May, 2020
No comments provided
Editorial decision: Minor revision
On 06 May, 2020
Review #2 received
Received 05 May, 2020
Reviewer #2 agreed
On 28 Apr, 2020
Review #1 received
Received 25 Apr, 2020
Editor assigned
On 23 Apr, 2020
Reviewers invited
Invitations sent on 23 Apr, 2020
Reviewer #1 agreed
On 23 Apr, 2020
Editor invited
On 22 Apr, 2020
First submitted
On 17 Apr, 2020
Submission checks complete
On 17 Apr, 2020
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Subject Areas
Nuclear Medicine & Medical Imaging
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This preprint is under consideration at EJNMMI Radiopharmacy and Chemistry. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Intravenous and oral copper kinetics, biodistribution and dosimetry in healthy humans studied by [64Cu]copper PET/CT
Kristoffer Kjærgaard
Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital; Department of Hepatology and Gastroenterology, Aarhus University Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6440-2784
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 01 Jun, 2020
Published
On 18 Jun, 2020
No community comments so far
Editorial decision: Accept
On 25 May, 2020
Editor assigned
On 24 May, 2020
Submission checks complete
On 23 May, 2020
Editor invited
On 23 May, 2020
No comments provided
Editorial decision: Minor revision
On 06 May, 2020
Review #2 received
Received 05 May, 2020
Reviewer #2 agreed
On 28 Apr, 2020
Review #1 received
Received 25 Apr, 2020
Editor assigned
On 23 Apr, 2020
Reviewers invited
Invitations sent on 23 Apr, 2020
Reviewer #1 agreed
On 23 Apr, 2020
Editor invited
On 22 Apr, 2020
First submitted
On 17 Apr, 2020
Submission checks complete
On 17 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Nuclear Medicine & Medical Imaging
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at EJNMMI Radiopharmacy and Chemistry.
Purpose: Copper is essential for enzymatic processes throughout the body. [64Cu]copper (64Cu) 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 64Cu in healthy humans by both intravenous and oral administration.
Methods: Six healthy participants underwent PET/CT studies with intravenous or oral administration of 64Cu. 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, 64Cu 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, 64Cu 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 64Cu in urine and faeces after intravenous administration was negligible. Hepatic removal kinetics showed that the clearance of 64Cu 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: 64Cu 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, and after oral administration, 64Cu is rapidly absorbed from the gastrointestinal tract and deposited primarily in the liver. Administration of 50 MBq 64Cu yielded images of high quality for both administration forms with radiation doses 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.
Figure 1
Figure 2
Figure 3