Biodistribution in rats and estimates of doses to humans from 64CuCl2, a potential theranostic tracer

Manrique-Arias, Juan C.; Carrasco-Hernández, Jhonatan; Reyes, Patricia Román; Ávila‐Rodríguez, Miguel A.

doi:10.1016/j.apradiso.2016.05.030

Cited by 11 publications

(5 citation statements)

References 18 publications

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“…We recently reported the biodistribution of [ 64 Cu]CuCl 2 in healthy rats and estimated radiation doses to humans by extrapolating the animal data [15]. As discussed in our previous publication, these results cannot be directly compared because the biodistribution data were obtained from different species, and the discrepancies in the results most probably reflect the differences among the species in size and metabolic rate as well as differences in the assumptions in the dose calculations [16].…”

Section: Discussionmentioning

confidence: 99%

Biodistribution and radiation dosimetry of [64Cu]copper dichloride: first-in-human study in healthy volunteers

et al. 2017

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BackgroundIn recent years, Copper-64 (T1/2 = 12.7 h) in the chemical form of copper dichloride ([64Cu]CuCl2) has been identified as a potential agent for PET imaging and radionuclide therapy targeting the human copper transporter 1, which is overexpressed in a variety of cancer cells. Limited human biodistribution and radiation dosimetry data is available for this tracer. The aim of this research was to determine the biodistribution and estimate the radiation dosimetry of [64Cu]CuCl2, using whole-body (WB) PET scans in healthy volunteers. Six healthy volunteers were included in this study (3 women and 3 men, mean age ± SD, 54.3 ± 8.6 years; mean weight ± SD, 77.2 ± 12.4 kg). After intravenous injection of the tracer (4.0 MBq/kg), three consecutive WB emission scans were acquired at 5, 30, and 60 min after injection. Additional scans were acquired at 5, 9, and 24 h post-injection. Low-dose CT scan without contrast was used for anatomic localization and attenuation correction. OLINDA/EXM software was used to calculate human radiation doses using the reference adult model.ResultsThe highest uptake was in the liver, followed by lower and upper large intestine walls, and pancreas, in descending order. Urinary excretion was negligible. The critical organ was liver with a mean absorbed dose of 310 ± 67 μGy/MBq for men and 421 ± 56 μGy/MBq for women, while the mean WB effective doses were 51.2 ± 3.0 and 61.8 ± 5.2 μSv/MBq for men and women, respectively.ConclusionsTo the best of our knowledge, this is the first report on biodistribution and radiation dosimetry of [64Cu]CuCl2 in healthy volunteers. Measured absorbed doses and effective doses are higher than previously reported doses estimated with biodistribution data from patients with prostate cancer, a difference that could be explained not just due to altered biodistribution in cancer patients compared to healthy volunteers but most likely due to the differences in the analysis technique and assumptions in the dose calculation.

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Section: Discussionmentioning

confidence: 99%

Biodistribution and radiation dosimetry of [64Cu]copper dichloride: first-in-human study in healthy volunteers

et al. 2017

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“…Nevertheless, the findings of age-dependent changes of 64 Cu accumulation in Atp7b −/− knockout mice support further study of age-dependent changes of cerebral copper fluxes in WD patients using [ 64 Cu]CuCl 2 -PET/CT imaging. Radiation dosimetry of [ 64 Cu]CuCl 2 estimated from preclinical biodistribution and radiation dosimetry studies in rodents [7, 8, 32] and clinical use of [ 64 Cu]CuCl 2 as a radiopharmaceutical for diagnostic imaging of prostate cancer in human [33] support safe use of [ 64 Cu]CuCl 2 as a tracer for evaluation of cerebral copper metabolism imbalance in WD patients. In view of a tiny amount of copper ions (< 0.04 ng/μCi of 64 CuCl 2 ) in a tracer dose of [ 64 Cu]CuCl 2 , there is little concern of copper toxicity on neurons when a tracer dose of [ 64 Cu]CuCl 2 is administered for PET/CT imaging in human.…”

Section: Discussionmentioning

confidence: 99%

Age-dependent changes of cerebral copper metabolism in Atp7b −/− knockout mouse model of Wilson’s disease by [64Cu]CuCl2-PET/CT

Xie

Pascual

et al. 2017

Metab Brain Dis

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Copper is a nutritional metal required for brain development and function. Wilson’s disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by mutation of ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study is to explore feasibility and use of copper-64 chloride ([64C]CuCl2) as a tracer for noninvasive assessment of age-dependence changes of cerebral copper metabolism in WD using an Atp7b−/− knockout mouse model of WD and a positron emission tomography/computed tomography (PET/CT) scanner. Continuing from recent study of biodistribution and radiation dosimetry of [64C]CuCl2 in Atp7b−/− knockout mice, PET quantitative analysis revealed low 64Cu radioactivity in the brains of Atp7b−/− knockout mice at 7th week of age, compared with the 64Cu radioactivity in the brains of age and gender-matched wild type C57BL/6 mice, at 24 hour (h) post intravenous injection of [64C]CuCl2 as a tracer. Furthermore, age-dependent increase of 64Cu radioactivity was detected in the brains of Atp7b−/− knockout mice from 13th to 21th week of age, using the data derived from a longitudinal [64C]CuCl2-PET/CT study of Atp7b−/− knockout mice with orally administered [64Cu]CuCl2 as a tracer. The findings of this study support the use of [64Cu]CuCl2-PET/CT as a tool for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD patients presenting with variable neurological and psychiatric symptoms.

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“…Relative 64 CuCl 2 kidney uptake was even higher from 30 min to 3 h p.i. in the study from Manrique-Arias et al in Wistar rats [ 25 ]. These data contrast with our observations, as kidneys were only the third most accumulating organ after the liver and intestines.…”

Section: Discussionmentioning

confidence: 99%

64CuCl2 PET Imaging of 4T1-Related Allograft of Triple-Negative Breast Cancer in Mice

et al. 2022

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64CuCl2 is an economic radiotracer for oncologic PET investigations. In the present study, we characterized the uptake of 64CuCl2 in vivo by µPET/CT in an allograft 4T1-related mouse model (BALB/c) of advanced breast cancer. 18F-FDG was used as a comparator. Twenty-two animals were imaged 7–9 days following 4T1-cell implantation inside mammary glands. Dynamic 64CuCl2 µPET/CT acquisition or iterative static images up to 8 h p.i. were performed. Animal biodistribution and tumor uptake were first evaluated in vivo by µPET analysis and then assessed on tissue specimens. Concerning 18F-FDG µPET, a static acquisition was performed at 15 min and 60 min p.i. Tumor 64CuCl2 accumulation increased from 5 min to 4 h p.i., reaching a maximum value of 5.0 ± 0.20 %ID/g. Liver, brain, and muscle 64CuCl2 accumulation was stable over time. The tumor-to-muscle ratio remained stable from 1 to 8 h p.i., ranging from 3.0 to 3.7. Ex vivo data were consistent with in vivo estimations. The 18F-FDG tumor accumulation was 8.82 ± 1.03 %ID/g, and the tumor-to-muscle ratio was 4.54 ± 1.11. 64CuCl2 PET/CT provides good characterization of the 4T1-related breast cancer model and allows for exploration of non-glycolytic cellular pathways potentially of interest for theragnostic strategies.

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Biodistribution in rats and estimates of doses to humans from 64CuCl2, a potential theranostic tracer

Cited by 11 publications

References 18 publications

Biodistribution and radiation dosimetry of [64Cu]copper dichloride: first-in-human study in healthy volunteers

Biodistribution and radiation dosimetry of [64Cu]copper dichloride: first-in-human study in healthy volunteers

Age-dependent changes of cerebral copper metabolism in Atp7b −/− knockout mouse model of Wilson’s disease by [64Cu]CuCl2-PET/CT

64CuCl2 PET Imaging of 4T1-Related Allograft of Triple-Negative Breast Cancer in Mice

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