Peripheral metabolism of [(18)F]FDDNP and cerebral uptake of its labelled metabolites.
[(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.
Luurtsema
Gert
G
Department of Nuclear Medicine and PET Research, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands. g.luurtsema@vumc.nl
Schuit
Robert C
RC
Takkenkamp
Kevin
K
Lubberink
Mark
M
Hendrikse
N Harry
NH
Windhorst
Albert D
AD
Molthoff
Carla F M
CF
Tolboom
Nelleke
N
van Berckel
Bart N M
BN
Lammertsma
Adriaan A
AA
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
C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; D005462:Fluorine Radioisotopes; D009570:Nitriles; D019275:Radiopharmaceuticals