PT  - JOURNAL ARTICLE
AU  - Seok Rye Choi
AU  - Geoff Golding
AU  - Zhiping Zhuang
AU  - Wei Zhang
AU  - Nathaniel Lim
AU  - Franz Hefti
AU  - Tyler E. Benedum
AU  - Michael R. Kilbourn
AU  - Daniel Skovronsky
AU  - Hank F. Kung
TI  - Preclinical Properties of <sup>18</sup>F-AV-45: A PET Agent for Aβ Plaques in the Brain
AID  - 10.2967/jnumed.109.065284
DP  - 2009 Nov 01
TA  - Journal of Nuclear Medicine
PG  - 1887--1894
VI  - 50
IP  - 11
4099  - http://jnm.snmjournals.org/content/50/11/1887.short
4100  - http://jnm.snmjournals.org/content/50/11/1887.full
SO  - J Nucl Med2009 Nov 01; 50
AB  - β-amyloid plaques (Aβ plaques) in the brain, containing predominantly fibrillary Aβ peptide aggregates, represent a defining pathologic feature of Alzheimer disease (AD). Imaging agents targeting the Aβ plaques in the living human brain are potentially valuable as biomarkers of pathogenesis processes in AD. (E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine (18F-AV-45) is such as an agent currently in phase III clinical studies for PET of Aβ plaques in the brain. Methods: In vitro binding of 18F-AV-45 to Aβ plaques in the postmortem AD brain tissue was evaluated by in vitro binding assay and autoradiography. In vivo biodistribution of 18F-AV-45 in mice and ex vivo autoradiography of AD transgenic mice (APPswe/PSEN1) with Aβ aggregates in the brain were performed. Small-animal PET of a monkey brain after an intravenous injection of 18F-AV-45 was evaluated. Results: 18F-AV-45 displayed a high binding affinity and specificity to Aβ plaques (Kd, 3.72 ± 0.30 nM). In vitro autoradiography of postmortem human brain sections showed substantial plaque labeling in AD brains and not in the control brains. Initial high brain uptake and rapid washout from the brain of healthy mice and monkey were observed. Metabolites produced in the blood of healthy mice after an intravenous injection were identified. 18F-AV-45 displayed excellent binding affinity to Aβ plaques in the AD brain by ex vivo autoradiography in transgenic AD model mice. The results lend support that 18F-AV-45 may be a useful PET agent for detecting Aβ plaques in the living human brain.