Dataset Information

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

ABSTRACT:

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, while 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 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.

SUBMITTER: Kjærgaard K

PROVIDER: S-EPMC7303253 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Kjærgaard Kristoffer K Sandahl Thomas Damgaard TD Frisch Kim K Vase Karina Højrup KH Keiding Susanne S Vilstrup Hendrik H Ott Peter P Gormsen Lars Christian LC Munk Ole Lajord OL

EJNMMI radiopharmacy and chemistry 20200618 1

<h4>Purpose</h4>Copper is essential for enzymatic processes throughout the body. [<sup>64</sup>Cu]copper (<sup>64</sup>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 <sup>64</sup>Cu in healthy humans by both intravenous and oral administration.<h4>Methods</h4>Six healthy ...[more]

PMID: 32556736

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Project description:Background & aimsIn Wilson disease (WD), copper accumulation and increased non-ceruloplasmin-bound copper in plasma lead to liver and brain pathology. To better understand the fate of non-ceruloplasmin-bound copper, we used PET/CT to examine the whole-body distribution of intravenously injected 64-copper (64Cu).MethodsEight patients with WD, five heterozygotes, and nine healthy controls were examined by dynamic PET/CT for 90 min and static PET/CT up to 20 h after injection. We measured 64Cu activity in blood and tissue and quantified the kinetics by compartmental analysis.ResultsInitially, a large fraction of injected 64Cu was distributed to extrahepatic tissues, especially skeletal muscle. Thus, across groups, extrahepatic tissues accounted for 45-58% of the injected dose (%ID) after 10 min, and 45-55% after 1 h. Kinetic analysis showed rapid exchange of 64Cu between blood and muscle as well as adipose tissue, with 64Cu retention in a secondary compartment, possibly mitochondria. This way, muscle and adipose tissue may protect the brain from spikes in non-ceruloplasmin-bound copper. Tiny amounts of cerebral 64Cu were detected (0.2%ID after 90 min and 0.3%ID after 6 h), suggesting tight control of cerebral copper in accordance with a cerebral clearance that is 2-3-fold lower than in muscle. Compared to controls, patients with WD accumulated more hepatic copper 6-20 h after injection, and also renal copper at 6 h.ConclusionNon-ceruloplasmin-bound copper is initially distributed into a number of tissues before being redistributed slowly to the eliminating organ, the liver. Cerebral uptake of copper is extremely slow and likely highly regulated. Our findings provide new insights into the mechanisms of copper control.Impact and implicationsMaintaining non-ceruloplasmin-bound copper within the normal range is an important treatment goal in WD as this "free" copper is considered toxic to the liver and brain. We found that intravenously injected non-ceruloplasmin-bound copper quickly distributed to a number of tissues, especially skeletal muscle, subcutaneous fat, and the liver, while uptake into the brain was slow. This study offers new insights into the mechanisms of copper control, which may encourage further research into potential new treatment targets.Clinical trial number2016-001975-59.

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Dataset Information

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

Purpose

Methods

Results

Conclusion

Trial registration number

Publications

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

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Dataset Information

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

Purpose

Methods

Results

Conclusion

Trial registration number

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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