title: Peripheral metabolism of [(18)F]FDDNP and cerebral uptake of its labelled metabolites.
abstract: [(18)F]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 [(18)F]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 [(18)F]FDDNP. After 10 min, more than 80% of plasma radioactivity was identified as polar (18)F-labelled fragments, probably formed from N-dealkylation of [(18)F]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.
authors.affiliation: Department of Nuclear Medicine and PET Research, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands. g.luurtsema@vumc.nl
authors.forename: Gert
authors.initials: G
authors.lastname: Luurtsema
authors.forename: Robert C
authors.initials: RC
authors.lastname: Schuit
authors.forename: Kevin
authors.initials: K
authors.lastname: Takkenkamp
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: N Harry
authors.initials: NH
authors.lastname: Hendrikse
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.forename: Carla F M
authors.initials: CF
authors.lastname: Molthoff
authors.forename: Nelleke
authors.initials: N
authors.lastname: Tolboom
authors.forename: Bart N M
authors.initials: BN
authors.lastname: van Berckel
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes; D006801:Humans; D009570:Nitriles / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; D005462:Fluorine Radioisotopes; D009570:Nitriles; D019275:Radiopharmaceuticals