Abstract
Two radiofluoro-pegylated phenylbenzoxazole derivatives, 4-(5-(2-(2-(2-[ 18F]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N- methylaniline ([ 18F]24) and 4-(5-(2-(2-(2-[ 18F] fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N,N-dimethylaniline ([ 18F]32), were synthesized and evaluated as probes for imaging cerebral β-amyloid (Aβ) plaques in living brain tissue by PET. [ 18F]24 and [ 18F]32 displayed high affinity for Aβ 1-42 aggregates (K i = 9.3 and 3.9 nM, respectively). In vitro autoradiography with sections of post-mortem AD brain and transgenic mouse brain confirmed the affinity of these tracers. Initial high uptake into and rapid washout from the brain in normal mice were observed. [ 18F]24 also displayed excellent binding to Aβ plaques in ex vivo autoradiographic experiments with Tg2576 mice. Furthermore, small-animal PET studies demonstrated significant differences in the clearance profile after the administration of [ 18F]24 between Tg2576 and wild-type mice. The results suggest [ 18F]24 to be a useful PET agent for detecting Aβ plaques in the living human brain.
| Original language | English |
|---|---|
| Pages (from-to) | 9136-9145 |
| Number of pages | 10 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 55 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - Nov 8 2012 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
Cite this
Novel 18F-labeled benzoxazole derivatives as potential positron emission tomography probes for imaging of cerebral β-amyloid plaques in alzheimers disease. / Cui, Mengchao; Ono, Masahiro; Kimura, Hiroyuki; Ueda, Masashi; Nakamoto, Yuji; Togashi, Kaori; Okamoto, Yoko; Ihara, Masafumi; Takahashi, Ryosuke; Liu, Boli; Saji, Hideo.
In: Journal of Medicinal Chemistry, Vol. 55, No. 21, 08.11.2012, p. 9136-9145.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel 18F-labeled benzoxazole derivatives as potential positron emission tomography probes for imaging of cerebral β-amyloid plaques in alzheimers disease
AU - Cui, Mengchao
AU - Ono, Masahiro
AU - Kimura, Hiroyuki
AU - Ueda, Masashi
AU - Nakamoto, Yuji
AU - Togashi, Kaori
AU - Okamoto, Yoko
AU - Ihara, Masafumi
AU - Takahashi, Ryosuke
AU - Liu, Boli
AU - Saji, Hideo
PY - 2012/11/8
Y1 - 2012/11/8
N2 - Two radiofluoro-pegylated phenylbenzoxazole derivatives, 4-(5-(2-(2-(2-[ 18F]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N- methylaniline ([ 18F]24) and 4-(5-(2-(2-(2-[ 18F] fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N,N-dimethylaniline ([ 18F]32), were synthesized and evaluated as probes for imaging cerebral β-amyloid (Aβ) plaques in living brain tissue by PET. [ 18F]24 and [ 18F]32 displayed high affinity for Aβ 1-42 aggregates (K i = 9.3 and 3.9 nM, respectively). In vitro autoradiography with sections of post-mortem AD brain and transgenic mouse brain confirmed the affinity of these tracers. Initial high uptake into and rapid washout from the brain in normal mice were observed. [ 18F]24 also displayed excellent binding to Aβ plaques in ex vivo autoradiographic experiments with Tg2576 mice. Furthermore, small-animal PET studies demonstrated significant differences in the clearance profile after the administration of [ 18F]24 between Tg2576 and wild-type mice. The results suggest [ 18F]24 to be a useful PET agent for detecting Aβ plaques in the living human brain.
AB - Two radiofluoro-pegylated phenylbenzoxazole derivatives, 4-(5-(2-(2-(2-[ 18F]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N- methylaniline ([ 18F]24) and 4-(5-(2-(2-(2-[ 18F] fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N,N-dimethylaniline ([ 18F]32), were synthesized and evaluated as probes for imaging cerebral β-amyloid (Aβ) plaques in living brain tissue by PET. [ 18F]24 and [ 18F]32 displayed high affinity for Aβ 1-42 aggregates (K i = 9.3 and 3.9 nM, respectively). In vitro autoradiography with sections of post-mortem AD brain and transgenic mouse brain confirmed the affinity of these tracers. Initial high uptake into and rapid washout from the brain in normal mice were observed. [ 18F]24 also displayed excellent binding to Aβ plaques in ex vivo autoradiographic experiments with Tg2576 mice. Furthermore, small-animal PET studies demonstrated significant differences in the clearance profile after the administration of [ 18F]24 between Tg2576 and wild-type mice. The results suggest [ 18F]24 to be a useful PET agent for detecting Aβ plaques in the living human brain.
UR - http://www.scopus.com/inward/record.url?scp=84868593540&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868593540&partnerID=8YFLogxK
U2 - 10.1021/jm300251n
DO - 10.1021/jm300251n
M3 - Article
C2 - 22690944
AN - SCOPUS:84868593540
VL - 55
SP - 9136
EP - 9145
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 21
ER -