Longitudinal Assessment of Cerebral β-Amyloid Deposition in Mice Overexpressing Swedish Mutant β-Amyloid Precursor Protein Using 18F-Florbetaben PET

被引：68

作者：

Rominger, Axel ^{[1
]}

Brendel, Matthias ^{[1
]}

Burgold, Steffen ^{[2
]}

Keppler, Kevin ^{[2
]}

Baumann, Karlheinz ^{[3
]}

Xiong, Guoming ^{[1
]}

Mille, Erik ^{[1
]}

Gildehaus, Franz-Josef ^{[1
]}

Carlsen, Janette ^{[1
]}

Schlichtiger, Juli ^{[1
]}

Niedermoser, Sabrina ^{[1
]}

Woengler, Bjoern ^{[1
]}

Cumming, Paul ^{[4
]}

Steiner, Harald ^{[5
,6
]}

Herms, Jochen ^{[2
]}

Haass-, Christian ^{[5
,6
,7
]}

Bartenstein, Peter ^{[1
,7
]}

机构：

[1] Univ Munich, Dept Nucl Med, D-81377 Munich, Germany

[2] Univ Munich, Dept Translat Brain Res, German Ctr Neurodegenerat Dis DZNE, D-81377 Munich, Germany

[3] F Hoffmann La Roche & Cie AG, pRED, Pharma Res & Early Dev, DTA CNS, Basel, Switzerland

[4] ABX, Radeberg, Germany

[5] Univ Munich, Adolf Butenandt Inst, D-81377 Munich, Germany

[6] German Ctr Neurodegenerat Dis DZNE, Munich, Germany

[7] Munich Cluster Syst Neurol SyNergy, Munich, Germany

来源：

JOURNAL OF NUCLEAR MEDICINE | 2013年 / 54卷 / 07期

关键词：

Alzheimer disease; beta-amyloid plaque load; small-animal PET; transgenic mouse model; F-18-florbetaben; DOPAMINE D-2/3 RECEPTORS; TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; IMAGING AGENTS; BRAIN; STILBENES; PLAQUES; BINDING;

D O I：

10.2967/jnumed.112.114660

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

The progression of beta-amyloid deposition in the brains of mice overexpressing Swedish mutant beta-amyloid precursor protein (APP-Swe), a model of Alzheimer disease (AD), was investigated in a longitudinal PET study using the novel beta-amyloid tracer F-18-florbetaben. Methods: Groups of APP-Swe and age-matched wild-type (WT) mice (age range, 10-20 mo) were investigated. Dynamic emission recordings were acquired with a small-animal PET scanner during 90 min after the administration of F-18-florbetaben (9 MBq, intravenously). After spatial normalization of individual PET recordings to common coordinates for mouse brain, binding potentials (BPND) and standardized uptake value ratios (SUVRs) were calculated relative to the cerebellum. Voxelwise analyses were performed using statistical parametric mapping (SPM). Histochemical analyses and ex vivo autoradiography were ultimately performed in a subset of animals as a gold standard assessment of beta-amyloid plaque load. Results: SUVRs calculated from static recordings during the interval of 30-60 min after tracer injection correlated highly with estimates of BPND based on the entire dynamic emission recordings. F-18-florbetaben binding did not significantly differ in APP-Swe mice and WT animals at 10 and 13 mo of age. At 16 mo of age, the APP-Swe mice had a significant 7.9% increase (P < 0.01) in cortical F-18-florbetaben uptake above baseline and at 20 mo there was a 16.6% increase (P < 0.001), whereas WT mice did not show any temporal changes in tracer uptake during the interval of follow-up. Voxelwise SPM analyses revealed the first signs of increased cortical binding at 13 mo and confirmed progressive binding increases in both the frontal and the temporal cortices (P < 0.001 uncorrected) to 20 mo. The SUVR strongly correlated with percentage plaque load (R = 0.95, P < 0.001). Conclusion: In the first longitudinal PET study in an AD mouse model using the novel beta-amyloid tracer F-18-florbetaben, the temporal and spatial progression of amyloidogenesis in the brain of APP-Swe mice were sensitively monitored. This method should afford the means for preclinical testing of novel therapeutic approaches to the treatment of AD.

引用

页码：1127 / 1134

页数：8

共 37 条

[31] ASYMMETRIC EXPRESSION PATTERNS OF BRAIN TRANSTHYRETIN IN NORMAL MICE AND A TRANSGENIC MOUSE MODEL OF ALZHEIMER'S DISEASE [J].