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

Abstract

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.

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

“…This difference is likely because of different analytical approaches rather than altered biodistribution of 64 Cu in patients with prostate cancer compared with healthy subjects. However, our results, based on the newest phantoms and tissue weighing factors [15][16][17], are in agreement with the observations made by Avila-Rodriguez et al in healthy participants [5].…”

“…[ 64 Cu]copper [1] ( 64 Cu) PET is characterized by high spatial resolution (positron range, 0.7 mm in water), and the radioactive half-life of 64 Cu (t 1/2 = 12.7 h) allows for in vivo assessment of copper biodistribution, even in compartments with slow copper turnover [4]. To date, only few 64 Cu PET studies of biodistribution and radiation dosimetry after intravenous injection in humans have been published, but it remains unclear which organs are the most critical in terms of radiation exposure [5][6][7]. In addition, no such studies have been published with oral administration of 64 Cu, the natural entrance route of copper in humans.…”

Hypoxia imaging and theranostic potential of [64Cu][Cu(ATSM)] and ionic Cu(II) salts: a review of current evidence and discussion of the retention mechanisms

“…An early study on the therapeutic effect of [ 64 Cu][Cu-(ATSM)] by Lewis et al suggested that the absorbed dose from Auger electrons is dependent on the distance between copper-64 ions and the cell nucleus, since the Auger electrons have low energy and very short range in tissue but can induce significant DNA damage in close proximity to the cell nucleus [46]. [101]. For a more comprehensive list of dosimetry estimations in different organs, we refer readers to the original article in reference [101].…”

“…[101]. For a more comprehensive list of dosimetry estimations in different organs, we refer readers to the original article in reference [101].…”

Calculations of dose point kernels of 64Cu in different media with PENELOPE Monte Carlo code

“…4 64 Cu can also be labeled with chelators which can be linked to monoclonal antibodies, proteins, peptides, and nanoparticles to image and treat a variety of clinical conditions and diseases. 5,6 Avila-Rodriguez et al 7 have studied the biodistribution of [ 64 Cu] CuCl 2 in six healthy volunteers (three men and three women) from serial whole-body PET/CT imaging after the radiopharmaceutical administration. The group has incorporated the biodistribution data into the dosimetry code: OLINDA/EXM (Organ Level Internal Dose Assessment Code, Vanderbilt University, Nashville, USA) 8 to assess the organ doses in a reference adult model: the critical organ was liver with an average absorbed dose of 310 AE 67 lGy/MBq for men and 421 AE 56 lGy/MBq for women.…”