Imaging of amyloid beta in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism.
BACKGROUND
Amyloid-beta (Abeta) plaque formation is a hallmark of Alzheimer's disease (AD) and precedes the onset of dementia. Abeta imaging should allow earlier diagnosis, but clinical application is hindered by the short decay half-life of current Abeta-specific ligands. (18)F-BAY94-9172 is an Abeta ligand that, due to the half-life of (18)F, is suitable for clinical use. We thus studied the effectiveness of this ligand in identifying patients with AD.


METHODS
15 patients with mild AD, 15 healthy elderly controls, and five individuals with frontotemporal lobar degeneration (FTLD) were studied. (18)F-BAY94-9172 binding was quantified by use of the standardised uptake value ratio (SUVR), which was calculated for the neocortex by use of the cerebellum as reference region. SUVR images were visually rated as normal or AD.


RESULTS
(18)F-BAY94-9172 binding matched the reported post-mortem distribution of Abeta plaques. All AD patients showed widespread neocortical binding, which was greater in the precuneus/posterior cingulate and frontal cortex than in the lateral temporal and parietal cortex. There was relative sparing of sensorimotor, occipital, and medial temporal cortex. Healthy controls and FTLD patients showed only white-matter binding, although three controls and one FTLD patient had mild uptake in frontal and precuneus cortex. At 90-120 min after injection, higher neocortical SUVR was observed in AD patients (2.0 [SD 0.3]) than in healthy controls (1.3 [SD 0.2]; p<0.0001) or FTLD patients (1.2 [SD 0.2]; p=0.009). Visual interpretation was 100% sensitive and 90% specific for detection of AD.


CONCLUSIONS
(18)F-BAY94-9172 PET discriminates between AD and FTLD or healthy controls and might facilitate integration of Abeta imaging into clinical practice.
Rowe
Christopher C
CC
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia. christopher.rowe@austin.org.au
Ackerman
Uwe
U
Browne
William
W
Mulligan
Rachel
R
Pike
Kerryn L
KL
O'Keefe
Graeme
G
Tochon-Danguy
Henry
H
Chan
Gordon
G
Berlangieri
Salvatore U
SU
Jones
Gareth
G
Dickinson-Rowe
Kerryn L
KL
Kung
Hank P
HP
Zhang
Wei
W
Kung
Mei Ping
MP
Skovronsky
Daniel
D
Dyrks
Thomas
T
Holl
Gerhard
G
Krause
Sabine
S
Friebe
Matthias
M
Lehman
Lutz
L
Lindemann
Stefanie
S
Dinkelborg
Ludger M
LM
Masters
Colin L
CL
Villemagne
Victor L
VL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000138:chemical synthesis; D001921:Brain / Q000000981:diagnostic imaging*; D003704:Dementia / Q000175:diagnosis / Q000000981:diagnostic imaging; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D013267:Stilbenes / Q000138:chemical synthesis
D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D013267:Stilbenes; C527756:4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene