Development and evaluation of compounds for imaging of beta-amyloid plaque by means of positron emission tomography.
OBJECTIVE
The proof of concept for in vivo targeting of beta-amyloid plaques (Abeta) in patients with Alzheimer's disease (AD) by means of nuclear imaging methods has been shown in recent clinical studies.


METHODS
For positron emission tomography (PET), the five compounds [(11)C]PIB, 3'[(18)F]FPIB, [(18)F]FDDNP, [(11)C]SB-13 and [(18)F]F-SB-13 have been developed by a formal charge neutralisation of agents used for staining of AD brain post mortem.


RESULTS
In AD-patients, these compounds have been shown to possess a selective uptake in the brain regions known to have a high Abeta-load. Progress towards tracers with proportionality between tracer uptake and quantity of Abeta-load, of use for longitudinal studies of AD patients, is addressed in the current development of Abeta-tracers.


CONCLUSIONS
Despite the extensive information on the structure-affinity relationship of several Abeta-binding compounds, data on the regional brain binding kinetics-beyond uptake in healthy rodents-have been obtained only for a few compounds. Recent results indicate that PET-imaging of Abeta-deposits in transgenic rodent models of AD is feasible which may be valuable for a more relevant preclinical evaluation of Abeta-tracers.
Henriksen
Gjermund
G
Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, München, Germany. G.Henriksen@lrz.tum.de
Yousefi
Behrooz H
BH
Drzezga
Alexander
A
Wester
Hans-Jürgen
HJ
D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D049268:Positron-Emission Tomography / Q000639:trends*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
D016229:Amyloid beta-Peptides; D019275:Radiopharmaceuticals