Intrathecal [64Cu]Cu-albumin PET reveals age-related decline of cerebrospinal fluid (CSF)-lymphatic efflux

Age–related cognitive decline is associated with dysfunctional lymphatic efflux of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. Intrathecal [64Cu]Cu–albumin positron emission tomography (PET) was applied in mice for the evaluation of lymphatic efflux of CSF and its age–related variation. [64Cu]Cu–albumin PET was done at multiple time points after intrathecal injection of [64Cu]Cu–albumin with the infusion speed of 700 nl/min in the adult and aged mice of 15–25 months old age. CSF clearance and paravertebral lymph nodes were quantified after injection and at later stationary phase. Representing perturbed state by 6 μl (1/7 of CSF volume with twice the production rate for 9 minutes of intrathecal injection) and at the next day of stationary return of CSF dynamics in mice, CSF clearance half–time from the subarachnoid space was 93.4 ± 19.7 in adult and 123.3 ± 15.6 minutes in aged mice (p = 0.01). The % injected dose at 4, 6 and 24 hours were higher in aged mice than in the adult mice (p < 0.05) and the visualized paravertebral lymph node activity tended to be lower in the aged, which was different from [64Cu]Cu-NOTA or [64Cu]Cu-ESION PET. [64Cu]Cu-albumin PET enabled quantification of CSF–lymphatic efflux over all the levels of brain spinal cords and visualization with quantifiability of lymph node activity. [64Cu]Cu-albumin PET revealed an age-related decrease in CSF–lymphatic efflux due to less efflux from the subarachnoid space, especially at stationary phase in the aged mice. ### Competing Interest Statement The authors have declared no competing interest.