Alteration of copper fluxes in brain aging: A longitudinal study in Rodent using ⁶⁴CuCl₂-PET/CT

Brain aging is associated with changes of various metabolic pathways. Copper is required for brain development and function, but little is known about changes in copper metabolism during brain aging. The objective of this study was to investigate alteration of copper fluxes in the aging mouse brain with positron emission tomography/computed tomography using ⁶⁴CuCl₂ as a radiotracer (⁶⁴CuCl₂-PET/CT). A longitudinal study was conducted in C57BL/6 mice (n = 5) to measure age-dependent brain and whole-body changes of ⁶⁴Cu radioactivity using PET/CT after oral administration of ⁶⁴CuCl₂ as a radiotracer. Cerebral ⁶⁴Cu uptake at 13 months of age (0.17 ± 0.05 %ID/g) was higher than the cerebral ⁶⁴Cu uptake at 5 months of age (0.11 ± 0.06 %ID/g, p < 0.001), followed by decrease to (0.14 ± 0.04 %ID/g, p = 0.02) at 26 months of age. In contrast, cerebral 18F-FDG uptake was highest at 5 months of age (7.8 ± 1.2 %ID/g) and decreased to similar values at 12 (5.2 ± 1.1 %ID/g, p < 0.001) and 22 (5.6 ± 1.1 %ID/g, p < 0.001) months of age. The findings demonstrated alteration of copper fluxes associated with brain aging and the time course of brain changes in copper fluxes differed from changes in brain glucose metabolism across time, suggesting independent underlying physiological processes. Hence, age-dependent changes of cerebral copper fluxes might represent a novel metabolic biomarker for assessment of human brain aging process with PET/CT using ⁶⁴CuCl₂ as a radiotracer.