Synthesis and evaluation of a radiofluorinated ketone body derivative.

The ketone bodies d-beta-hydroxybutyric acid and acetoacetic acid represent the principal oxidative energy sources of most tissues when dietary glucose is scarce. An F-labeled ketone body could be a useful tool for studying ketone body metabolism using positron emission tomography (PET). Here, we report the first radiofluorinated ketone body derivative (3)-4-[F]fluoro-3-hydroxybutyric acid ([F]FBHB) as well as its enantiomer and l-beta-hydroxybutyric acid derivative, (3)-4-[F]fluoro-3-hydroxybutyric acid (()-[F]F3HB). PET imaging in mice showed biodistribution profiles of the radiotracers that were consistent with the biodistribution of the respective endogenous compounds. Moreover, both enantiomers visualized breast cancer xenografts . Fasting over 24 h showed significantly enhanced brain and heart uptake of [F]FBHB and tumor uptake of ()-[F]F3HB. Disorders exhibiting altered energy substrate utilization, such as Alzheimer's disease, epilepsy, diabetes, and cancer may be of interest for PET imaging studies using [F]FBHB.