A brain uptake study of [1-(11)C]hexanoate in the mouse: the effect of hypoxia, starvation and substrate competition.

We evaluated the potential of sodium [1-(11)C]hexanoate (11C-HA) as a radiopharmaceutical with which to assess oxidative metabolism of the brain by PET. 11C-HA, sodium [1-(14)C]acetate and [3H]deoxyglucose were simultaneously injected into mice under control, hypoxic and starving conditions. In the control, the brain uptake of 11C was maximal at 3 min (% ID/g = 2.2-2.5), being twice as high as that of 14C, followed by a gradual clearance. The time-radioactivity curve of 11C was similar to that of 14C. Hypoxia enhanced the brain uptake of 3H, but not of either 11C or 14C. Starvation enhanced the brain uptake of 3H and 11C. The clearance rate of 11C was not significantly affected by either condition. In the control brain at 3 min postinjection of HA, 65% of the total radioactivity was detected as labeled glutamate and glutamine, which was gradually decreased by 47% at 30 min. The brain to blood ratios of 11C-HA at 3 min were significantly reduced by butyrate, hexanoate and octanoate loading but not by that with other monocarboxylic acids or ketone bodies.