Peripheral metabolism of [18F]FDDNP and cerebral uptake of its labelled metabolites

[18F]FDDNP is a positron emission tomography (PET) tracer for determining amyloid plaques and neurofibrillary tangles in the brain in vivo. In order to quantify binding of this tracer properly, a metabolite-corrected plasma input function is required. The purpose of the present study was to develop a sensitive method for measuring [18F]FDDNP and its radiolabelled metabolites in plasma. The second aim was to assess whether these radiolabelled metabolites enter the brain.In humans, there was extensive metabolism of [18F]FDDNP. After 10 min, more than 80% of plasma radioactivity was identified as polar 18F-labelled fragments, probably formed from N-dealkylation of [18F]FDDNP. These labelled metabolites were reproduced in vitro using human hepatocytes. PET studies in rats showed that these polar metabolites can penetrate the blood–brain barrier and result in uniform brain uptake.