Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson’s disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found insubstantia nigraand caudate nucleus of Parkinson’s disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson’s disease; for instance, it is known that CTR1 is decreased insubstantia nigra pars compactain Parkinson’s disease and that a mutation in ATP7B could be associated with Parkinson’s disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology.

In 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. The 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. To 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.