Role of 64CuCl2 PET/CT in staging of prostate cancer

Capasso, Enza; Durzu, Silvia; Piras, Sara; Zandieh, Shahin; Kabos, Peter; Haug, Alexander; Hacker, Marcus; Meleddu, C; Mirzaei, Siroos

doi:10.1007/s12149-015-0968-4

Cited by 60 publications

(87 citation statements)

References 15 publications

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“…However, what is clear is that the extrapolation of animal (mice and rats) data to humans’ incorrectly identify the critical organ, and underestimate radiation absorbed doses for [ 64 Cu]CuCl 2 . Radiation dosimetry estimates of [ 64 Cu]CuCl 2 using biodistribution data from patients with prostate cancer [8] are also underestimated compared to dose estimates based on biodistribution data obtained from healthy volunteers. The difference of radiation-absorbed doses to specific organs and effective doses presented in Table 3 could be explained in part by the altered biodistribution of [ 64 Cu]CuCl 2 in prostate cancer patients, as it has been demonstrated that the biodistribution of 64 Cu in tumor-bearing animals is altered as compared with that of the corresponding control animals [17, 18], but given the subjectivity of the process of curve fitting, volume drawing, and assumptions in the dose calculations, the differences between our results and those previously reported by Capasso et al are most likely not just due to altered biodistribution but due to the analysis technique.…”

Section: Discussionmentioning

confidence: 99%

“…Future clinical applications of [ 64 Cu]CuCl 2 will require accurate dosimetric data, especially for therapeutic procedures; however, only limited human biodistribution data and organ dosimetry are currently available for this radionuclide in the chemical form of copper chloride. Capasso et al obtained human biodistribution data from patients with prostate cancer and estimated radiation doses, but the main purpose of Capasso’s research was not to perform the dosimetry but to investigate the role of [ 64 Cu]CuCl 2 PET/CT in staging of prostate cancer [8]. The dosimetric calculations were performed with limited data points, which limit the confidence in the data curve-fitting for determining the time-integrated activity coefficients in source organs.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

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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“…Age-dependent changes of brain copper fluxes in Atp7b −/− knockout WD mice was demonstrated by a longitudinal PET study using orally administered 64 CuCl 2 as a radiotracer [64]. Moreover, 64 CuCl 2 was successfully used as a radiotracer for diagnostic imaging of prostate cancer [65] and brain tumors [66] in humans with PET, based on previous use of 64 CuCl 2 as a tracer for localization of human prostate cancer xenograft tumors in rodents [67]. The findings from these studies support use of 64 CuCl 2 as a radiotracer for quantitative analysis of age-dependent changes of copper fluxes in brain aging and pathophysiology of AD with PET [68–70].…”

Section: Coppermentioning

confidence: 99%

Radiopharmaceuticals for Assessment of Altered Metabolism and Biometal Fluxes in Brain Aging and Alzheimer’s Disease with Positron Emission Tomography

Xie

Peng

2017

JAD

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Aging is a risk factor for Alzheimer’s disease (AD). There are changes of brain metabolism and biometal fluxes due to brain aging, which may play a role in pathogenesis of AD. Positron emission tomography (PET) is a versatile tool for tracking alteration of metabolism and biometal fluxes due to brain aging and AD. Age-dependent changes in cerebral glucose metabolism can be tracked with PET using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG), a radiolabeled glucose analogue, as a radiotracer. Based on different patterns of altered cerebral glucose metabolism, 18F-FDG PET was clinically used for differential diagnosis of AD and Frontotemporal dementia (FTD). There are continued efforts to develop additional radiopharmaceuticals or radiotracers for assessment of age-dependent changes of various metabolic pathways and biometal fluxes due to brain aging and AD with PET. Elucidation of age-dependent changes of brain metabolism and altered biometal fluxes is not only significant for a better mechanistic understanding of brain aging and the pathophysiology of AD, but also significant for identification of new targets for the prevention, early diagnosis and treatment of AD.

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Role of 64CuCl2 PET/CT in staging of prostate cancer

Abstract: The preliminary results of this study show a high uptake of (64)CuCl2 in PC and involved regional lymph nodes indicating to a great potential of (64)CuCl2 PET/CT for primary staging of patients with prostate cancer.

Cited by 60 publications

References 15 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

Radiopharmaceuticals for Assessment of Altered Metabolism and Biometal Fluxes in Brain Aging and Alzheimer’s Disease with Positron Emission Tomography

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