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

Journal of Nuclear Medicine

Juli Schlichtiger¹  Guoming Xiong¹  Paul Cumming¹  Franz-Josef Gildehaus¹  Harald Steiner¹  Matthias Brendel¹  Sabrina Niedermoser¹  Christian Haass¹  Karlheinz Baumann¹  Jochen Herms¹  Björn Wängler¹  Peter Bartenstein¹  Steffen Burgold¹  Kevin Keppler¹  Axel Rominger¹  Erik Mille¹  Janette Carlsen¹ 

关键词: Alzheimer disease;    β-amyloid plaque load;    small-animal PET;    transgenic mouse model;    ¹⁸F-florbetaben;   

DOI  :  10.2967/jnumed.112.114660

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

The progression of β-amyloid deposition in the brains of mice overexpressing Swedish mutant β-amyloid precursor protein (APP-Swe), a model of Alzheimer disease (AD), was investigated in a longitudinal PET study using the novel β-amyloid tracer 18F-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 18F-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 β-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. 18F-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 18F-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 β-amyloid tracer 18F-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.

【 授权许可】

Unknown