Influence of peripheral metabolic state on [18F]FDG brain uptake in mice

Objectives While [18F]FDG is widely used as a tracer for brain activity in preclinical imaging, there is no accordance on the effect of metabolic conditioning. In this study, we evaluated how different pre-scanning experimental setups influence FDG biodistribution in vivo.

Methods A total of 33 healthy C57Bl/6 inbred mice were investigated in 7 groups: (1) control, (2) oxygen in isoflurane anesthesia replaced by medical air, (3) 4hr fasting, (4) 18hr fasting, (5) insulin/glucose pretreatment(I/G), (6) I/G and isoproterenol (Iso), and (7) ketamine/xylazine (K/X). Thirty-five min after onset of anesthesia 7.70±0.76 MBq FDG was injected via tail vein. Dynamic PET scans (60 min) were performed using a dedicated INVEON scanner. Blood glucose was measured serially.

Results In mice fasted 4 or 18 hrs or receiving isoflurane in medical air, blood glucose levels remained stable and FDG uptake was unchanged in brain as well as in all other investigated organs. I/G ± Iso resulted in hypoglycemia (90% reduction of blood glucose) and increased myocardial and brown fat FDG uptake, but did not change brain FDG uptake significantly. K/X caused hyperglycemia (127% increase of blood glucose), suppressed myocardial and brown fat uptake, and resulted in a significant decrease of brain uptake by 42% vs control (SUV 1.55±0.13 vs 0.90±0.15; p<0.05).

Conclusions Under isoflurane anesthesia and in contrast to peripheral organs, brain [18F]FDG uptake in healthy mice is stable across various metabolic conditions, including fasting and insulin stimulation. Ketamine/xylazine reduces brain FDG uptake, either due to neurosuppression or due to a nonlinear effect of elevated blood glucose levels. This should be taken into account for the experimental setup of metabolic studies.