Evaluation of [76Br]FBAU 3′,5′-dibenzoate as a lipophilic prodrug for brain imaging

[Br-76]FBAU is a potential PET tracer for assessing proliferation. This Study proposes that [Br-76]FBAU 3',5'-dibenzoate has higher blood-brain-barrier permeability than [Br-76]FBAU itself and thus might be better suited for applications in the brain. The brain uptake indexes of the two compounds measured after carotid injection (29.6 +/- 13.9 for [Br-76]FBAU 3'.5'-dibenzoate. versus 10.0 +/- 8.7 for [Br-76] FBAU) support this claim. Biodistribution studs also showed that the brain accumulation of activity was higher in rats injected with [Br-76] FBAU 3',5'-dibenzoate than with [Br-76]FBAU (0.119+/-0.023 DUR at 1 h, versus 0.061 +/- 0.006). [Br-76]FBAU 3'.5'-dibenzoate was relatively stable in rat plasma. gradually being hydrolyzed to [Br-76]FBAU exponentially with a calculated half-life of 0.8 h. DNA incorporation of [Br-76]FBAU was also confirmed. The results presented support the hypothesis that the 3',5'-dibenzoate can act as a prodrug for FBAU and deliver more radiolabeled nucleoside to the brain. (C) 2002 Elsevier Science Inc. All rights reserved.