Radiation dosimetry estimates of 64CuCl2 based on biodistribution data of rats

Objectives Over the last few years, ⁶⁴Cu in the chemical form of CuCl₂ has shown potential as a theranostic agent, however, limited biodistribution and dosimetry data is available for this tracer. The aim of this study was to obtain the biodistribution of ⁶⁴CuCl₂ in healthy rats and to perform an estimation of the radiation dosimetry extrapolating the animal data to humans.

Methods High specific activity ⁶⁴Cu (150-700 GBq/μmol) was produced via cyclotron using the ⁶⁴Ni(p,n) reaction. After intravenous administration of ⁶⁴CuCl₂ (37-74 MBq), serial microPET imaging and biodistribution studies were carried out in Wistar rats at 0.5, 1, 3, 5 and 24 h post-injection of the tracer. The animal biodistribution data (%ID/g) were extrapolated to human values (a 57-kg female and a 73-kg male) using the percent kg/g method, and radiation absorbed doses and effective doses were calculated based on the RADAR method using the OLINDA/EXM 1.1 software.

Results Serial microPET imaging revealed a rapid clearance from blood and a high uptake in kidneys, liver and bowels, which was consistent with biodistribution data, suggesting metabolic activity of copper in these organs. No uptake in the brain was observed and the elimination by urine was negligible. Dosimetric estimations for humans revealed the lower large intestine (LLI) wall as the critical organ with a mean (all subjects, mean and women) absorbed dose of 132±47 µGy/MBq (mean±SEM), followed by the osteogenic cells, kidneys and small intestine with mean absorbed doses of 94.1±24.5, 74.5±18.5, and 56.1±12.0 µGy/MBq, respectively. On the other hand, the mean effective dose for ⁶⁴CuCl₂ in humans was estimated to be 43.0±5.7 µSv/MBq.

Conclusions It remains to be determined whether ⁶⁴Cu in the chemical form of ⁶⁴CuCl₂ will be used as a theranostic agent in humans; however, some discordances of the currently available radiation dosimetry estimates based on biodistribution data from different species, warrant a human dosimetric study with healthy controls to ensure accurate dosimetry values and to determine dose-limiting organs. Research Support: This research was supported by CONACYT Grant 179218 and UNAM-DGAPA-PAPIIT IT201115.